Subject: Life Sciences, Biophysics Keywords: non-ionizing radiation; millimeter waves; novel biomedical applications; yeast; non-invasive devices
Online: 17 September 2020 (07:08:47 CEST)
Nonionizing millimeter-waves (MMW) are reported to interact with cells in a variety of ways. Possible mechanisms of the inhibited cell division effect were investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm2 safety standards. ~1.0 mW/cm2 exposure over 5-6 hours treatment on 50 cells/μl samples of Saccharomyces cerevisiae model organism, resulted in 62% growth rate reduction compared to control (sham). The effect was specific for 85-105 GHz range and energy dose and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deletion cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm2) and compared to that of a compact waveguide (17.17 mW/cm2) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. Combinations of MMW mediated Structure Resonant Energy Transfer (SRET), membrane modulations eliciting signaling effects, and energetic resonance with biomolecules were indicated to be responsible for the observations reported. Our results provide novel mechanistic insights enabling innovative applications of nonionizing radiation procedures for eliciting targeted biomedical outcomes.
ARTICLE | doi:10.20944/preprints202008.0577.v2
Subject: Physical Sciences, Acoustics Keywords: quantum diode; quantum gate element; novel superconductivity; bias current; memorization property; quantum correlation
Online: 17 November 2020 (12:50:24 CET)
Two opposed p–n diodes are connected with another junction that causes cancellation of the electric field in the depletion layer of each diode by the field of the other diode. This derived quantum diode is called the A system. Another dual diode, constructed by the same process but with the p- and n-types positioned as duality, called the B system. When a bias voltage is applied between the A and B systems, Lorentz conservation imparts a momentum (i.e., a wave number) to the carriers in the absence of any internal voltage. Thus, a superconducting bias current density appears without the need for cooling. The reappearances of electron–hole pairs on the junction surfaces are assumed to be described by entire wavefunctions normalized by the band gap. Based on the bias superconducting current, NOT and NAND gates were constructed from the quantum diode systems. Numerical calculations revealed that the constant phases of the entire wavefunctions of the p-and n-types converged. Accordingly, it was clarified that Bose–Einstein condensation and the Meissner effect (described by the London equation) occurred in the quantum diode systems. Moreover, the systems exhibited rectification characteristics and a switching speed of the order of 10-14 s. Combining this switching property with the large bias superconducting current (of the order of several V), we developed NOT and NAND gates with direct quantum correlations among many qubits, which are unaffected by random and thermal noises. These gates have memorization and initialization properties and are compatible with existing and accumulating programing algorithms. Moreover, when harvesting a divergent current output from these systems, the bias superconducting current and memorization property preserve the formed quantum correlations.
ARTICLE | doi:10.20944/preprints201909.0204.v1
Subject: Medicine & Pharmacology, Other Keywords: Office of Innovation; novel drugs; novel therapies; regulatory science; Latin American Regulatory landscape
Online: 18 September 2019 (12:51:16 CEST)
Regulatory agencies across the Latin American Region have strengthened the regulatory science through the development of new tools, standards and various other related parameters to evaluate and assess safety, efficacy, quality and performance. The former have been implemented to promote and incorporate new drugs and technologies, which still, are a challenge to well-established regulatory frameworks. Furthermore, in today’s environment, the existing regulatory framework protecting public’s health creates barriers for market entry of novel drugs and medical devices. This article aims to the pioneering work that Cuban Regulatory Agency (CECMED) has been developing with the aim to build a strong regulatory framework geared to accelerated innovation and the successful transition from research and development to clinical development. The Office of Innovation recently established at the CECMED is the first flagship in Latin America and the Caribbean region. Its aim is to play a leading role as a driving force for the national and regional biopharmaceutical innovation. This article will discuss the Office of Innovation its conceptualisation and management taking into account the Latin American regional and national Cuban context.
ARTICLE | doi:10.20944/preprints202208.0091.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Parkinson’s disease; novel tetracycline; neuroprotection
Online: 3 August 2022 (12:08:08 CEST)
The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its po-tential use in long-term neuroprotective treatments. Here, we synthesized a DMC derivative with residual antibiotic activity and improved neuroprotective effects. The molecule, called de-rivative demeclocycline (DDMC), was obtained by the removal of both dimethylamino substitu-ents at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-SynPFF ) in ex vitro models and in SH-SY5Y-α-Syn-tRFP cells. In addition, in the presence of DDMC, α-SynPFF were less inflammogenic, as they dampened the release of tumor necrosis factor α (TNF-α) and glutamate by microglial cells compared to control fibrils. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in PD and other synucleinopathies.
ARTICLE | doi:10.20944/preprints202203.0367.v1
Online: 28 March 2022 (14:30:09 CEST)
Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.
ARTICLE | doi:10.20944/preprints202002.0359.v1
Online: 25 February 2020 (05:18:22 CET)
During December 2019, a novel coronavirus named as 2019-nCoV, has emerged in Wuhan, China. The human to human transmission of this virus has also been established. Untill now the virus has infected more than seven thousand people and has spread to fifteen countries. The World Health Organization (WHO) has declared 2019-nCoV as global health emergency due to its outburst well beyond China. There is need to develop some vaccines or therapeutics to control or prevent 2019-nCoV infections. The bottleneck with current conventional approaches is that these require longer time for vaccine development. However, computer assisted approaches help us to produce effective vaccine in short time compared with conventional methods. In this study, bioinformatics analysis was used to predict B cell and T cell epitopes of surface glycoprotein of 2019-nCoV that could be suitable to trigger significant immune response. The sequence of surface glycoprotein was collected from the database and analyzed to identify the immunogenic epitope. Both B cell and T cell epitopes were analyzed so the predicted epitopes can stimulate both cellular and humoral immune responses. We predicted 13 B cell and 05 T cell epitopes that later on were joined with GPGPG linker to make a single peptide. This computational approach to design a multi epitope peptide vaccine against emerging 2019-nCoV allows us to find novel immunogenic epitopes against the antigen targets of surface 2019-nCoV surface glycoprotein. This multi epitope peptide vaccine may prove effective to combat 2019-nCoV infections.
ARTICLE | doi:10.20944/preprints202002.0179.v1
Online: 14 February 2020 (02:34:55 CET)
Ongoing outbreak of pneumonia caused by novel coronavirus (2019-nCoV) began in December 2019 in Wuhan, China, and the number of new patients continues to increase. On the contrary to ongoing outbreak in China, however, there are limited secondary outbreaks caused by exported case outside the country. We here conducted simulations to estimate the impact of potential secondary outbreaks at a community outside China. Simulations using stochastic SEIR model was conducted, assuming one patient was imported to a community. Among 45 possible scenarios we prepared, the worst scenario resulted in total number of persons recovered or removed to be 997 (95% CrI 990-1,000) at day 100 and maximum number of symptomatic infectious patients per day of 335 (95% CrI 232-478). Calculated mean basic reproductive number (R0) was 6.5 (Interquartile range, IQR 5.6-7.2). However, with good case scenarios with different parameter led to no secondary case. Altering parameters, especially time to hospital visit could change the impact of secondary outbreak. With this multiple scenarios with different parameters, healthcare professionals might be able to prepare for this viral infection better.
ARTICLE | doi:10.20944/preprints202111.0197.v1
Online: 10 November 2021 (08:53:05 CET)
Gelatinization of starch content in pet foods can be impacted by several factors including moisture, retention time, and ingredients used. Starch gelatinization has been associated with digestibility but isn’t well studied using ingredients common in non-traditional canine diets. The objective of this research was to examine the impacts of dietary ingredient profile (traditional vs non-traditional) and assess impacts to total starch content and starch gelatinization. Traditional diets (n = 10) utilizing meat-based ingredients including chicken, chicken by-product meal, meat and bone meal and plant-based ingredients including rice, barley, oats, and corn were examined in comparison with non-traditional diets (n = 10) utilizing meat-based ingredients including alligator, buffalo, venison, kangaroo, squid, quail, rabbit, rabbit and salmon along with plant-based ingredients including tapioca, peas, chickpeas, lentils, potato, and pumpkin. Representative samples were collected via grab sample technique (5 samples/diet) and were assessed for total starch content as well as percent starch gelatinization. Difference between ingredient type was assessed using a Students t-test in SAS 9.4. Significance was set at P < 0.05. Distribution of total starch content based on ingredient type (traditional vs non-traditional) revealed that mean total starch content was higher in traditional diets as compared to non-traditional diets (P <0.0001). Conversely, starch gelatinization was found to be higher in non-traditional diets (P < 0.0001). Total starch content and total gelatinized starch had a strong negative correlation (P < 0.01) in traditional diets, though no correlation was observed in non-traditional diets. This negative correlation indicates a decrease in total gelatinized starch associated with increased total starch content. These novel data reveal important differences between starch content and gelatinization and could impact manufacturing processes for ingredient types as well as feeding recommendations. Unpredicted variation between ingredient formulations could potentially lead to decreased digestibility and absorption and may result in nutrient deficiencies.
ARTICLE | doi:10.20944/preprints202004.0267.v1
Subject: Medicine & Pharmacology, Other Keywords: novel coronavirus; COVID-19; epidemic model; epidemiology
Online: 16 April 2020 (08:24:07 CEST)
Italy was the first country in Europe which imposed control measures of travel restrictions, quarantine and contact precautions to tackle the epidemic spread of the novel coronavirus (SARS-CoV-2) in all its regions. While such efforts are still ongoing, uncertainties regarding SARS-CoV-2 transmissibility and ascertainment of cases make it difficult to evaluate the effectiveness of restrictions. Here, we employed a Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model to assess SARS-CoV-2 transmission dynamics, working on the number of reported patients in intensive care unit (ICU) and deaths in Sicily (Italy), from 24 February to 13 April. Overall, we obtained a good fit between estimated and reported data, with a small fraction of unreported SARS-CoV-2 cases (19.5%; 95%CI=0%-34.7%) before 10 March lockdown. Interestingly, we estimated that the first set of restrictions reduced transmission rate in the community by 42% (95%CI=38%-46%), and that more stringent measures adopted on 23 March succeeded to drastically curb the transmission rate by 84% (95%CI=80%-88%). Thus, our estimates delineated the characteristics of SARS-CoV2 epidemic before restrictions taking into account unreported data. Further modeling after the adoption of control measures, moreover, indicated that restrictions reduced SARS-CoV2 transmission considerably.
ARTICLE | doi:10.20944/preprints202004.0052.v1
Subject: Medicine & Pharmacology, Other Keywords: novel coronavirus; epidemiology; COVID-19; epidemic model
Online: 6 April 2020 (12:30:42 CEST)
In the midst of the novel coronavirus (SARS-CoV-2) epidemic, examining reported case data could lead to biased speculations and conclusions. Indeed, estimation of unreported infections is crucial for a better understanding of the current emergency in China and in other countries. In this study, we aimed to estimate the unreported number of infections in China prior to 23 March 2020 restrictions. To do that, we developed a Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model which estimated unreported cases and infections from the reported number of deaths. Our approach relied on the fact that observed deaths were less likely to be affected by reporting biases than reported infections. Interestingly, we estimated that R0 was 2.43 (95%CI= 2.42 – 2.44) at the beginning of the epidemic, and that 92.9% (95%CI= 92.5% - 93.1%) of total cases were not reported. Similarly, the proportion of unreported new infections by day ranged from 52.1% to 100%, with a total of 91.8% (95%CI= 91.6% - 92.1%) unreported infections. Agreement between our estimates and those from previous studies proved that our approach was reliable to estimate prevalence and incidence of undocumented SARS-CoV2 infections. Once tested on Chinese data, our model could be applied on other countries with different surveillance and testing policies.
ARTICLE | doi:10.20944/preprints202002.0132.v2
Subject: Life Sciences, Virology Keywords: 2019-nCoV; SARS-CoV-2; novel corona virus; Wuhan pneumonia
Online: 18 February 2020 (11:52:25 CET)
The rapid development of 2019-2020 Wuhan seafood market pneumonia currently posed a major public health concern in China. Genome sequencing identified a novel beta-coronavirus closely related to SARS-CoV, named 2019-nCoV by WHO, as the cause of this pandemic disease. Viruses with single stranded RNA genome are prone to evolve quickly by accumulation of mutations, such as SNV, INDEL and cross viral recombination, aiding fast transmission among hosts and cross species. Here we collected related genome sequences and investigated variations shared by different strains of 2019-nCoV, identified reoccurrence of SNV mutations in clusters of patients, an indication of rapid evolution of 2019-nCoV at the transmission from animal host to human. The information collected herein would help to understand the dynamics of current pandemic.
ARTICLE | doi:10.20944/preprints202207.0157.v1
Subject: Life Sciences, Microbiology Keywords: Methylococcaceae; methanotroph; Indian rice field; Methylmonas; novel species
Online: 11 July 2022 (09:56:06 CEST)
An aerobic methanotroph, strain Kb3T, was isolated from a rhizospheric soil sample collected from a tropical Indian rice field. The cells were motile, Gram-negative bacilli, formed pink colonies and pink turbid/pellicles in the liquid medium. Biochemical characteristics showed that strain Kb3T utilised only methane and methanol as its sole carbon and energy sources. The isolate's 16S rRNA gene sequence expressed 99.52% similarity to the recently described valid species Methylomonas fluvii EbB (Mmf), with 92% query cover. But examining the genome similarity between Kb3 and EbB, a DDH value of 44.20% [41.6 - 46.7%] and an Ortho-ANI value of 91.48 was observed that were below the current cut-off values for species differentiation. Also, the 16S rRNA gene phylogeny and the phylogenomic analysis branched the two species separately. The major fatty acid in Methylomonas sp. Kb3 was C14:0, followed by C16:1 ω5c. The genome sequence revealed the size of strain Kb3 is 5.1 Mb, with the G + C content of 51.8%. Strain Kb3T shared the closest relatedness with Methylomonas sp. LW13 reveals a 99.66% 16S rRNA gene similarity, an Ortho-ANI value of 97.9%, a DDH value of 87.3%, and a close branching in the phylogenomic tree Kb3 and LW13 together form a new species. The genomic and phylogenetic distinction between species Mmf and strain Kb3 supports Kb3T to be described as a novel species within the genus Methylomonas, with the proposed name, Methylomonas aquatica sp. nov. (Mma) and the type strain being Kb3T (=MCC 4012, =JCM 33634, =KCTC 72521).
ARTICLE | doi:10.20944/preprints202009.0446.v1
Subject: Medicine & Pharmacology, Other Keywords: Novel coronavirus diseases 2019; vaccination; target population; China
Online: 19 September 2020 (05:02:54 CEST)
All countries are facing decisions about which groups to prioritise for COVID-19 vaccination after the first vaccine product has been licensed, at which time supply shortages are inevitable. Here we define the key target populations and their size in China for a phased introduction of COVID-19 vaccination with evolving goals, accounting for the risk of illness and transmission. Essential workers (47.2 million) like healthcare workers could be prioritized for vaccination to maintain essential services. Subsequently, older adults, individuals with underlying health conditions and pregnant women (616.0 million) could be targeted to reduce severe COVID-19 outcomes. Then it could be further extended to target adults without underlying health conditions and children (738.7 million) to reduce symptomatic infections and/or to stop virus transmission. The proposed framework could assist Chinese policy-makers in the design of a vaccination program, and could be generalized to inform other national and regional COVID-19 vaccination strategies.
Online: 12 March 2020 (03:02:03 CET)
Novel coronavirus infection is a recent infective agent that causes severe potentially fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to the clinical presentation of solid organ transplant recipients are scarce. Two cases of novel coronavirus infection in two recipients of renal transplant with variable clinical presentations and outcomes are reported. The first patient presented with progressive respiratory symptoms, acute renal failure, and passed away, whereas the second one, although presented with respiratory tract symptoms and hypoxemia remained stable and exhibited an excellent clinical recovery despite recent reception of thymoglobulin induction. This paper reports rare cases of novel coronavirus infection in renal transplant recipients. For an enhanced insight of the novel coronavirus infection and acute kidney injury on the clinical presentation, severity, and outcome in solid organ transplant recipients, further investigations are required.
REVIEW | doi:10.20944/preprints201909.0222.v1
Subject: Life Sciences, Genetics Keywords: hearing impairment; novel murine genes; gene enrichment; africa
Online: 19 September 2019 (11:27:27 CEST)
The prevalence of congenital hearing impairment (HI) is highest in Africa. Estimates evaluated genetic causes to account for 31% of HI cases in Africa, but the identification of associated causative genes mutations have been challenging. In this study, we reviewed the potential roles, in humans, of 38 novel genes identified in a murine study. We gathered information from various genomic annotation databases and performed functional enrichment analysis using online resources i.e. genemania and g.proflier. Results revealed that 27/38 genes are express mostly in the brain, suggesting additional cognitive roles. Indeed, HERC1- R3250X had been associated with intellectual disability in a Moroccan family. A homozygous 216-bp deletion in KLC2 was found in two siblings of Egyptian descent with spastic paraplegia. Up to 27/38 murine genes have link to at least a disease, and the commonest mode of inheritance is autosomal recessive (n=8). Network analysis indicates that 20 other genes have intermediate and biological links to the novel genes, suggesting their possible roles in HI. This study will contribute to advance our knowledge in unravelling the biological roles of novel murine HI genes in humans and could enhance the understanding of the genetic causes of HI in Africans.
ARTICLE | doi:10.20944/preprints201807.0372.v1
Subject: Biology, Plant Sciences Keywords: novel lncRNA; lncRNA conservation; copaifera; epigenetics; adaptive response
Online: 20 July 2018 (04:31:16 CEST)
LncRNA are involved in multiple regulatory pathways, its versatile mode of action has disclosed a new layer in gene regulation. They are reportedly modulated during plant development, with specific tissue functions and in response to stresses. In this study, we analyzed LncRNA from leave samples collected from the legume Copaifera langsdorffii (copaiba) from two divergent ecosystems: Cerrado (CER) and Atlantic Rain Forest (ARF). We identified 8020 novel lncRNAs, from which 2893 transcripts were regulated above 2-fold and 566 above 5-folds in either condition. This putative lncRNA set was compared with seven Fabaceae genomes, of which 1747 and 1879 transcripts (from ARF and CER, respectively) aligned to at least two genomes. Further, 2194 copaiba lncRNAs were successfully mapped to at least one of six Fabaceae transcriptomes. The secondary structures of the lncRNAs that were conserved and differentially expressed between the populations were predicted using in silico methods. Our results indicate the potential involvement of lncRNAs in the adaptation of C. langsdorffii to two different biomes.
ARTICLE | doi:10.20944/preprints202209.0143.v1
Subject: Life Sciences, Microbiology Keywords: Salmonella; novel antibacterial agents; cannabidiol; co-therapy; bacterial genetics
Online: 12 September 2022 (09:55:22 CEST)
New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species it is important to examine potential interaction between CBD and common therapeutics such as broad-spectrum antibiotics. Here, we show that CBD-antibiotic co-therapy can effectively fight S. typhimurium via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics for potential antibiotic-CBD co-therapy. In this study, we reveal that Salmonella typhimurium (S. typhimurium) growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating Salmonella typhimurium.
ARTICLE | doi:10.20944/preprints202205.0407.v1
Subject: Biology, Plant Sciences Keywords: Fusarium; tomato; novel effector candidates; cell death; Nicotiana benthamiana
Online: 31 May 2022 (03:20:05 CEST)
Fusarium oxysporum f. sp. lycopersici (Fol) causes vascular wilt disease in tomato. Upon colonization of the host, Fol secretes many small effector proteins into the xylem sap to facilitate infection. Besides known SIX (Secreted In Xylem) proteins, the identity of additional effectors that contribute to Fol pathogenicity remains largely unexplored. We have performed a deep RNA-sequencing analysis of Fol race 2-infected tomato, used the sequence data to annotate a published genome assembly generated via PacBio SMRT sequencing of the Fol race 2 reference strain Fol4287, and analysed the resulting transcriptome to identify Fol effector candidates among the newly annotated genes. We examined the Fol-infection expression profiles of all 13 SIX genes present in Fol race 2 and identified 27 new candidate effector genes that were likewise significantly upregulated upon Fol infection. Using Agrobacterium-mediated transformation, we tested the ability of 22 of the new candidate effector genes to suppress or induce cell death in leaves of Nicotiana benthamiana. One effector candidate designated Fol-EC19, encoding a secreted guanyl-specific ribonuclease, was found to trigger cell death and two effector candidates designated Fol-EC14 and Fol-EC20, encoding a glucanase and a secreted trypsin, respectively, were identified that can suppress Bax-mediated cell death. Remarkably, Fol-EC14 and Fol-EC20 were also found to suppress I-2/Avr2- and I/Avr1-mediated cell death. Using the yeast secretion-trap screening system, we showed that these three biologically-active effector candidates each contain a functional signal peptide for protein secretion. Our findings provide a basis for further understanding the virulence functions of Fol effectors.
REVIEW | doi:10.20944/preprints202205.0024.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Outbreak; novel; unknown hepatitis; unknown aetiology; public health promotion
Online: 5 May 2022 (08:02:13 CEST)
Several clusters and individual cases of acute —often severe— hepatitis have been reported in Europe —mainly in the United Kingdom (U.K.)—, the United States (U.S.) and recently in Asia since October 2021. Laboratory investigation of the common viral hepatitis agents (HAV, HBV, HCV, HDV and HEV) yielded negative results prompting the use of the term “acute non hepA–E hepatitis” to describe this condition. The cases were characterized by the manifestations of acute hepatitis (abdominal pain, vomiting, diarrhea, jaundice and very high levels of liver enzymes) affecting children with a median age of 3–4 years. The exact underlying etiology has not been revealed yet; however, a leading hypothesis is that an infectious agent is the culprit underlying cause or at least a risk factor for acute non hepA–E hepatitis occurrence. So far, laboratory testing has shown the presence of adenovirus serotype 41 (Ad–41) which is classified in group F of adenoviruses in about three-fourths of the reported cases. However, the definitive link between adenoviruses and acute non hepA–E hepatitis has not been fully elucidated, which necessitates further investigation of this possible correlation. As of the end of April 2022, more than 200 cases were reported worldwide, the majority of which were in Europe: the U.K. (n=114), Italy (n=17), Spain (n=13), Israel (n=12), the U.S. (n=9), Denmark (n=6), Netherlands and Ireland (n=4), Japan (n=3), Austria, Belgium, France, and Norway (n=2), Germany, Poland, and Romania (n=1). Possible cases are being evaluated in Illinois, Minnesota, North Carolina, Wisconsin states of the U.S., Canada, Singapore and Slovenia. Vigilant surveillance and epidemiologic investigation to identify further cases are warranted at the global level to delineate the features of this emergent public health issue. The possible role of environmental and toxic agents including foodborne toxins should not be overlooked as well. Specific guidelines for identification of further cases is necessary particularly in low-income settings where testing for adenoviruses is not considered routinely. Genetic analysis of Ad–41 isolates is recommended to assess the potential changes in virus genome with subsequent possible altered virus behavior. Immunopathogenesis is another possibility that should be examined as well considering the absence of virus detection in liver biopsies of the affected children in the U.S.
REVIEW | doi:10.20944/preprints202004.0321.v1
Subject: Life Sciences, Biotechnology Keywords: 2019 Novel Coronavirus; plants; antiviral compounds; plant recombinant vaccines
Online: 19 April 2020 (04:15:18 CEST)
The proposal of novel drugs and approaches for effective treatment of the novel coronavirus is a necessity after the quick outbreak of the disease. Since the commencement of the coronavirus spread, enormous efforts have been made to protect, alleviate and cure the disease, though no specific treatment has been approved. While there have been convincing results in the use of chemical drugs and interferon therapy, such therapeutic approaches have various drawbacks and lack the required performance for the treatment of the new coronavirus. Medicinal plant species can provide a solution as a source of natural antiviral compounds by the accumulation of secondary metabolites and lectins as well as acting as a platform to express the viral immunogenic proteins. This study reviews the advantages and the results of previous research for the treatment of the novel coronavirus disease and previous generations of similar coronaviruses. Several plant-derived anti coronavirus compounds have been nominated that could be targeted for further research due to the similarity of the coronavirus disease in 2003 and the current coronavirus. This review regards plant species such as Scutellaria baicalensis (Baikal skullcap), and Utrica dioica (Stinging nettle) as suitable candidates for the new coronavirus antiviral research. Furthermore, the use of plants such as Nicotiana tabacum (Tobacco) for the expression of the coronavirus viral antigens can be a target for the future vaccinal research of the new coronavirus due to the efficiency of expression and intrinsic antiviral properties.
ARTICLE | doi:10.20944/preprints202001.0173.v1
Subject: Life Sciences, Microbiology Keywords: wetlands; methanotrophs; India; tropical; novel species; Type Ib; Methylotetracoccus
Online: 16 January 2020 (11:51:52 CET)
We enriched and isolated a novel gammproteobacterial methanotroph; strain FWC3, from tropical freshwater wetland, near Nagaon beach, Alibag, India. FWC3 is a coccoid, flesh pink/peach pigmented, non-motile methanotroph and the cells are present in pairs and as tetracocci. The culture can grow on methane (20%) as well as on a wide range of methanol from concentrations (0.02%-5%). Based on the comparison of genome data, FAME analysis, morphological characters and biochemical characters, FWC3 belongs to the tentatively and newly but not validly described genus ‘Methylotetracoccus’ of which only a single species strain was described, Methylotetracoccus oryzae C50C1. The ANI index between FWC3 and C50C1 strains is 94%, and the DDH value is 55.7%, less than the cut-off values 96% and 70%, respectively. The genome size of FWC3 is smaller (3.4 Mbp) compared to that of C50C1 (4.8 Mbp). Additionally, the FAME profile of FWC3 shows differences in cell wall fatty acid profiles compared to Methylotetracoccus oryzae C50C1. Also, there are other differences on the morphological, physiological and genomic levels. We propose FWC3 to be a member of a novel species of the genus Methylotetracoccus, for which the name Methylotetracoccus aquaticus is proposed. Also, an amended description of the genus Methylotetracoccus gen. nov. is given here. FWC3 is available in two international culture collections with the accession numbers: MCC 4198 (Microbial Culture collection, India) and JCM 33786 (Japan Collection of Microorganisms, Japan).
ARTICLE | doi:10.20944/preprints202209.0004.v2
Subject: Life Sciences, Virology Keywords: phage Rih21; MRSA; novel bacteriophage; S. aureus; bacteriophage; phage genome analysis
Online: 5 October 2022 (10:13:04 CEST)
From the hospital wastewater, a novel bacteriophage was isolated and characterized. According to characterization properties, this bacteriophage belongs to the Siphoviridae family, the maximum bacteriophage titer was recorded at 37°C and a pH of 7.2, had a 44,789 bp linear double-strand DNA genome, and within the genome sequence, there are 61 genes, all of which are encoded into proteins. Although this bacteriophage does not have any virulence factors or antimicrobial resistance genes and had specific lytic activity against some antimicrobial resistance S. aureus clinical isolates.
ARTICLE | doi:10.20944/preprints202012.0444.v1
Subject: Biology, Anatomy & Morphology Keywords: novel rumen yeast; screening; isolation; biomass of yeast; cellulase enzyme
Online: 18 December 2020 (07:26:28 CET)
We hypothesized that rumen fluid with yeast producing cellulase enzyme can occur and also produces a high biomass compared to S. cerevisiae. Therefore, the aim of this study was to screen and isolate yeast from rumen fluids with an experimental design method. We optimized a fermentation medium containing sugarcane molasses as a carbon source and urea as a nitrogen source to measure the efficiency of biomass production and cellulase activity. Two fistulated-crossbred Holstein Friesian steers, averaging 350 ± 20 kg body weight, were used to screen and isolate ruminal yeast. The two experiments were designed. A 12 × 3 × 3 factorial was used in a completely randomized design to determine biomass and carboxymethyl cellulase activity. Factor A was isolated yeasts and S. cerevisiae. Factor B was sugarcane molasses (M) concentration. Factor C was urea (U) concentration. Potential yeast was selected for identified and analyzed as a 4 × 3 factorial use in a completely randomized design including. Factor A was incubation times. Factor B was isolated yeast strains including code H-KKU20 (as P. kudriavzevii-KKU20), I-KKU20 (C. tropicalis-KKU20), and C-KKU20 (as Galactomyces sp.-KKU20). Isolation was under aerobic conditions, resulting in a total of 11 different colonies. We noted two appearances of colonies including, asymmetric colonies of isolated yeast (indicated as A, B, C, E, and J) and ovoid colonies (coded as D, F, G, H, I, and K). The highest biomass was observed in three yeasts including codes H, I, and C-KKU20 when inoculated in 25% molasses with 1% urea (M25+U1) (p <0.01). The highest CMCase activity was observed in yeast code H-KKU20 when inoculated in all media solutions (p <0.01). Ruminal yeasts strains H-KKU20, I-KKU20, and C-KKU20 were selected for their ability to produce biomass and their CMCase enzyme synthesis. Identification of isolates H-KKU20 and I-KKU20 revealed that those isolates belonged to Pichia kudriavzevii-KKU20 and Candida tropicalis-KKU20, while C-KKU20 was identified as Galactomyces sp.-KKU20. Two strains provided maximum cell growth: P. kudriavzevii-KKU20 (9.78 and 10.02 Log cell/ml) and C. tropicalis-KKU20 (9.53 and 9.6 Log cells/ml) at 60 and 72 h of incubation time, respectively. The highest ethanol production was observed in S. cerevisiae: 76.4, 77.8, 78.5, and 78.6 g/L at 36, 48, 60, and 72 h of incubation time, respectively (p <0.01). The P. kudriavzevii-KKU20 yielded the least reducing sugar about 30.6 and 29.8 g/L at 60 and 72 h of incubation time, respectively. It could be concluded that screening and isolating yeast from rumen fluids resulted in 11 different characteristics of yeasts. The first novel yeasts discovered in the rumen fluid of cattle were Pichia kudriavzevii-KKU20, Candida tropicalis-KKU20, and Galactomyces sp.- KKU20. P. kudriavzevii-KKU20 had higher results than the other yeasts in terms of biomass production, cellulase enzyme activity, and cell number.
BRIEF REPORT | doi:10.3390/sci2030055
Online: 14 July 2020 (00:00:00 CEST)
The world is currently facing a serious pandemic of coronavirus disease 2019 (COVID-19) which started in Wuhan, China, and was then transmitted rapidly to other countries. Countries applied different methods and procedures in an attempt to prevent or reduce and/or control the incidence of cases and manage existing ones. This paper discusses the methods and procedures applied by Kuwait to control this epidemic, and how effective they have been. The State of Kuwait followed WHO, European CDC, US CDC, and/or other countries’ institutional guidelines, and is still working on containing the disease, given the rising number of cases among Kuwaitis returning from affected areas such as the UK and USA, and migrant workers who bear the highest burden, given their cramped living conditions.
REVIEW | doi:10.20944/preprints202006.0157.v1
Subject: Keywords: novel coronavirus; SARS-CoV-2; COVID-19; pneumonia; Betacoronavirus; transmission
Online: 14 June 2020 (03:06:15 CEST)
The emergence of novel coronavirus (SARS-CoV-2) in marked as the highest pathogenic coronavirus that has crossed from the hosts to the human population in the twenty-first century. The spreading of COVID-19 in different chinese cities and around the world is travel-related viral spread with the unprecedented nosocomial outbreaks. It has also shown with high case-fatality rates, indeed to urgent prophylactic and therapeutic settings. Scientific advancements of the SARS-CoV-2 pandemic allowed for rapid progress to understand the epidemiology and pathogenesis of SARS-CoV-2. This review highlights the the genomic structure of SARS-CoV-2 with the proposed roles of genotype and phenotype of SARS-CoV-2 in pathogenesis and discuss recent results supporting treatment strategies of COVID-19 with a special focus on how these new insights may facilitate rational development of SARS-CoV-2 for targeted therapies in the future.
ARTICLE | doi:10.20944/preprints202003.0206.v2
Subject: Medicine & Pharmacology, Other Keywords: 2019 novel coronavirus infection; corons; SARS-CoV; interferon; systems biology
Online: 23 March 2020 (10:27:57 CET)
As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases. CoV can impede the interferon induction in humans. Moreover, STAT1, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γ combination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.
HYPOTHESIS | doi:10.20944/preprints202002.0254.v2
Subject: Medicine & Pharmacology, Other Keywords: 2019-nCoV; novel coronavirus pneumonia; docking; ACE2; viral main protease
Online: 23 February 2020 (02:09:52 CET)
The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.
ARTICLE | doi:10.20944/preprints202105.0308.v1
Subject: Biology, Anatomy & Morphology Keywords: Indonesia; biodiversity; novel antibiotics; drug screening; bioactivity; gene cluster networking; GNPS
Online: 13 May 2021 (14:05:00 CEST)
Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two-thirds of all clinically used antibiotics. Thus, exploiting Indonesia’s microbial diversity for actinomycetes may lead to the discovery of novel antibiotics. A total of 422 actinomycete strains were isolated from three different unique areas in Indonesia and tested for their antimicrobial activity. Nine potent bioactive strains were prioritized for further drug screening approaches. The nine strains were cultivated in different solid and liquid media and a combination of genome mining analysis and mass spectrometry (MS)-based molecular networking was employed to identify potential novel compounds. By correlating secondary metabolite gene cluster data with MS-based molecular networking results, we identified several gene cluster-encoded biosynthetic products from the nine strains, including naphthyridinomycin, amicetin, echinomycin, tirandamycin, antimycin, and desferrioxamine B. Besides, eight putative ion clusters and numerous gene clusters were detected that could not be associated with any known compound, indicating that the strains can produce novel secondary metabolites. Our results demonstrate that sampling of actinomycetes from unique and biodiversity-rich habitats, such as Indonesia, along with a combination of gene cluster networking and molecular networking approaches, accelerates natural product identification.
ARTICLE | doi:10.20944/preprints202104.0385.v1
Subject: Life Sciences, Biochemistry Keywords: antibiotic resistance; antimicrobial susceptibility testing; novel diagnostics; polymicrobial; sputum; drug resistant
Online: 14 April 2021 (14:21:15 CEST)
For polymicrobial infections, AtbFinder utilizes a novel paradigm of the population response to antibiotics, enabling bacterial growth in the form of a mixed microbial community and selecting the antibiotics targeting not only the principal pathogen, but also those bacteria that support their growth. TGV medium allowed culturing a more diverse set of bacteria from polymicrobial biospecimens, compared with that achieved with the standard media and enabled, already within 4h, accurate selection of the antibiotics that completely eliminated all cultivatable bacteria from clinical samples. In conclusion, AtbFinder system may be a valuable tool in improving antibiotic selection, enabling targeted empirical therapy and accurate antibiotic replacement, which is especially important in high-risk patients.
ARTICLE | doi:10.20944/preprints202008.0730.v1
Subject: Social Sciences, Business And Administrative Sciences Keywords: risk management and early measures; Novel Corona Virus (COVID-2019); GHS
Online: 31 August 2020 (17:56:33 CEST)
This research paper is mainly aimed to elaborate the initial risk management and measures which government of Pakistan took towards Novel Corona Virus (COVID-2019). This initial response and planning was devised after the early outbreak of COVID-2019 in Wuhan, China in early time of January 2020. Pakistan devised a comprehensive plan that not to evacuate their student from Wuhan, China. The government of Pakistan in compliance with the National Institute of Health (NIH) devised and documented comprehensive plans such as the flight operations postponed related to Umerah pilgrims, which were intended to go to sacred places of KSA (The Kingdom of Saudi Arabia). The process of visa, immigration policy totally changed and the government of Pakistan notified it officially that, no new visas of visit, student, and business would be issued in due course of uncertainty due to COVID-2019. The government of Pakistan also announced medical emergency and notified through the country’s provinces the process of testing and treatment of COVID-2019. The government of Pakistan also allocated funds for medical supplies and named out the particular country’s best laboratories. The government of Pakistan also locked down all the cities with the emergency announcement that people should stay inside the home in quarantine or self-isolation. NIH (The National Institute of Health) played a vital role in executing the planning to cope with COVID – 2019). The National Institute of Health responded as “The Centre for Disease Control”. In aid to the government, the national army of Pakistan responded in a proactive manner towards planed execution. The medical corps of Pakistan army dedicated themselves to treat the suspected patients of COVID – 2019. Due to plans, policies being documented, implemented in such a way productive way that from February 28, 2020 to till date there is not much critical situation and issues are not present. There are much productive results as there is not much boom in a rise of COVID-2019 patients. This lockdown under the authority of the provinces resulted in fruitful outcomes. Background: On January 02, 2020, authorities of the People Republic of China elaborated that they have encountered with a novel type of infectious viral disease 2019. Later on January 12, the authorities from China elaborated the related sequence of Corona Virus diseases 2019 names as COVID – 2019. When COVID-2019 being identified in Wuhan, Hubei China, as an early response the Government of Pakistan in support of the National Institute of Health (Field Epidemiology & Disease Surveillance Division) published a health advisory about novel coronavirus. Methods: According to Global Health Security Index, Pakistan is ranked as 105th country among 195 countries in GHS index. Overall Score of Pakistan is 35.5. The score of Early Detection and Reporting for Epidemics of Potential International Concern is 41.7. A Graphical depiction of the COVID-19 cases placed until April 10, 2020 as well as a graph trend line of recovered as well as death rate is also depicted. According to the graphical facts of Government of Pakistan and World meters, the recovery rate of COVID-19 is about 98 percent and 2.1 percent death rate is reported against the total cases. Trend analysis with line graph was drawn based on available data from official dashboard web portal of the government of Pakistan and worldometers.info. Data figures were incorporated from March to August 18, 2020 in MS Excel and then subsequently deployed to draw trend analysis from managing risk to recovery. Results: The line graph showed a slowdown in the COVID-19 cases and high rate of recoveries from COVID-19 in Pakistan. On March 11, 2020, there were 20 confirmed cases of coronavirus reported in Pakistan. No death was recorded in very first seven days, on March 18, 2020 only two deaths were reported. On August 18, 2020, there were 272128 recoveries, 6201 deaths, total confirmed cases 290445, and total test were 2340072 in Pakistan. As a results, we can report that due to early measures taken by government of Pakistan no mass scale destruction in terms of death and cases been recorded in Pakistan. Conclusions: To till date, the government of Pakistan tried its level best to minimize the coronavirus cases as much as they can. However, the ending of the potential attack of an outbreak would depend upon the well organized and coordinated approach at all levels such as true directed decisions, fully preparedness, as well implementation and evaluation of continuous decisions. As the recovery rate of the cases is 98 percent and merely death rate is 2.1 percent, concluded that in future it would be a good sign to stop the potential outbreak. Also, lock down as well as precautionary measurement taken by the provincial governments resulted a decline number of COVID-19 cases in the country. Another good sign is that merely 4 percent population of Pakistan is of more than 60 years of old it can be concluded that there are less chances of mass death due to outbreak of COVID-19.
REVIEW | doi:10.20944/preprints202006.0350.v1
Subject: Life Sciences, Biotechnology Keywords: Antibodies engineering; Computational approach; Novel drugs; Synthetic immunology; Next generation antibodies
Online: 28 June 2020 (20:24:49 CEST)
In the pre era of synthetic antibodies, pharmaceutical companies depend on finding novel drugs from medicinal plants and other traditional resources; while in present, technological advances in biology, computer and robotics give the researchers the ability to rewrite and edit DNA in order to synthesize very large sets of drug candidates; these novel and improved candidates serves the basis for creating another library of drug candidates and so on until we find the right biomolecule for the disease of interest. all these technologies combined together to synthesize therapeutic antibodies for many types of cancer, autoimmune diseases, and infectious diseases, that can address diseases much more readily to very rapidly get therapeutics into patients so that we can potentially have an impact on disease. The antibodies mechanism is recognize and bind to disease cells and pinpoint the immune system to attack those cells effectively. Now a days, they dependent on computational approach to guide and accelerate the process of antibodies engineering by combination of selection system and use of high-throughput data acquisition and analysis to build and construct populations of next generation antibodies that are thermo-stable, non-immunogenic as possible, and to be administered to many humans as possible. In this review, I will discuss the latest in silico methods for antibodies engineering.
REVIEW | doi:10.20944/preprints202004.0511.v1
Online: 29 April 2020 (13:43:54 CEST)
The current coronavirus disease 2019 (COVID-19) pandemic is largely driven by community transmission, after 2019 novel Coronavirus (2019-nCoV or SARS-CoV-2) crosses the borders. To stop the spread, rapid testing is required at community clinics and hospitals. These rapid tests should be comparable with the standard PCR technology. Isothermal amplification technology provides an excellent alternative that is highly amenable to resource limited settings, where expertise and infrastructure to support PCR are not available. In this review, we provide a brief description of isothermal amplification technology, its potential and the gaps that need to be considered for SARS-CoV-2 detection. Among this emerging technology, loop mediated amplification (LAMP) and recombinase polymerase amplification (RPA) technologies have been identified as potential platforms that could be implemented at community level, without samples referral to a centralised laboratory and prolonged turn-around-time associated with the standard COVID-19 RT-PCR test. LAMP, for example, has recently been shown to be comparable with PCR and could be performed in less than 30 min by non-laboratory staff, without RNA extractions commonly associated with PCR. More so, it is cost effective and could easily be scaled up to resource limited settings. Diagnostics developers, scientific community and commercial companies could consider this alternative method to help stop the spread of COVID-19.
REVIEW | doi:10.20944/preprints202004.0189.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Coronavirus; SARS CoV; SARS CoV-2; novel CoV; India
Online: 12 April 2020 (09:17:16 CEST)
COVID-19 disease outbreak was started in the December, 2019 in the Wuhan city of China which is also known as the largest transportation hub of China. During the spring festival of China the situation become epidemic. Soon, the virus is imported to many regions including the low income countries. Till now, 234073 infected reported cases of the COVID-19 in the world with the total of 9840 deaths (March 20, 2020). The common symptoms of the COVID-19 are the cough, high fever, sore throat, fatigue and breathlessness. The disease is found to be mild in most of the people, some of cases reported to the pneumonia also with multi organ dysfunction and acute ARDS (acute respiratory distress syndrome). It is found that the incubation period for the infection is 2-14 days which is usually 4 days in maximum of cases. India has reported 283 cases of COVID-19 infections till now with 4 deaths. India is still at stage 2 on local transmission as per WHO report 60. WHO reported 60 clearly stated that there is no community transmission occurred in India yet which can be prevented by the avoiding mass gathering and proper screening of the people. Govt. of India has taken many initiatives to minimize the spread of COVID-19 infection in the country. The infection rate of the COVID-19 in India remains low related to population size of the country. It is because of fast government action to quarantine the suspected people and shut down all its borders. There is a great slowdown in the global economy due to COVID-19 attack which is likely to costs around $1 trillion. The spread of COVID-19 infection can be reduced by minimizing the H-H transmissions. Still there is need of Anti-n-CoV drug development which can replace the supporting therapies for the treatment of infection.
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Novel coronavirus pneumonia; COVID-19; SARS-CoV-2; Pathology; Critical patient
Online: 9 March 2020 (10:31:10 CET)
Background Critical patients with novel coronavirus pneumonia ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis on gross examination. The haemorrhagic necrosis was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis, and partly hyaline degeneration, variable degrees of hemorrhagic pulmonary infarction. Small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma cells infiltrating into pulmonary interstitium. Bronchiolitis and alveolitis with proliferation, atrophy, desquamation and squamous metaplasia of epithelial cells. Atrophy, vacuolar degeneration, proliferation, desquamation and squamous metaplasia in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease.
ARTICLE | doi:10.20944/preprints202211.0380.v1
Subject: Life Sciences, Genetics Keywords: Heat stress response; novel transcripts; RNA-Sequencing; blood; liver; adrenal glands; rats
Online: 21 November 2022 (07:18:32 CET)
The molecular mechanisms underlying heat stress tolerance in animals to high temperatures remain unclear. This experiment was performed with Sprague-Dawley rats housed at 22 ℃ (control group; CT), and 42 ℃ for 30 min (H30), 60 min (H60), and 120 min (H120). Transcriptomic analysis using RNA-Sequencing (RNA-Seq) from blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120) was performed. The differentially expressed mRNA isoforms (DEIs) were identified and annotated by the CLC Genomics Workbench. Biological process and metabolic pathway analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A total of 225, 5,764, and 4,988 DEIs in the blood, liver, and adrenal glands were observed. Furthermore, the number of novel differentially expressed transcript lengths with annotated genes and the novel differentially expressed transcript with non-annotated genes were 136 and 8 in blood, 3,549 and 120 in the liver, as well as 3,078 and 220 in adrenal glands, respectively. A total of 35 genes were involved in the heat stress response, out of which Dnaja1, LOC680121, Chordc1, AABR07011951.1, Hsp90aa1, Hspa1b, Cdkn1a, Hmox1, Bag3 and Dnaja4 were commonly identified in the liver and adrenal glands, suggesting that these genes may regulate heat stress response through interactions between liver and adrenal glands. The results suggest that the identified mRNA isoforms could be considered as potential candidates for selecting mammals to improve thermotolerance.
REVIEW | doi:10.20944/preprints202202.0052.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cervical cancer; endometrial cancer; ovarian cancer; 2021 update; novel targeted therapies; immunotherapy
Online: 3 February 2022 (13:02:11 CET)
This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year [the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting]. Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecologic malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.
ARTICLE | doi:10.20944/preprints202011.0032.v3
Subject: Life Sciences, Biochemistry Keywords: Non-ionizing Radiation; Millimeter waves; Novel biomedical applications; Yeast; Non-invasive devices
Online: 16 April 2021 (14:52:04 CEST)
Nonionizing millimeter-waves (MMW) interact with cells in a variety of ways. Here the inhibited cell division effect was investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm2 safety standards. Irradiation using a power density of about 1.0 mW/cm2 , SAR over 5-6 hours on 50 cells/μl samples of Saccharomyces cerevisiae model organism resulted in 62% growth rate reduction compared to the control (sham). The effect was specific for 85-105 GHz range, and was energy and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deleted cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause permanent genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm2) and compared to that of a compact waveguide (17.17 mW/cm2) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. We have shown that non-thermal MMW radiation has potential for future use in treatment of yeast related diseases and other targeted biomedical outcomes.
COMMUNICATION | doi:10.20944/preprints202003.0395.v2
Subject: Life Sciences, Biotechnology Keywords: Novel coronavirus (SARS-CoV-2); RdRp; HCV; beclabuvir; in silico; molecular docking
Online: 2 April 2020 (11:25:57 CEST)
Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25o C beclabuvir, a non-nucleoside inhibitor of the RdRpHCV can efficiently bind to RdRp SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for binding of beclabuvir to RdRpSARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRpSARS-CoV-2 (ΔGvina = -8.0 kcal mol-1) than that observed with the Thumb 1 domain of RdRpHCV (ΔGvina = -7.1 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549th to 776th amino acid residues of RdRpSARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRpSARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.
REVIEW | doi:10.20944/preprints202003.0197.v3
Subject: Biology, Other Keywords: Built Environment (BE); building operations; novel coronavirus; COVID-19; SARS-CoV-2
Online: 2 April 2020 (05:19:41 CEST)
With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE) mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics.
COMMUNICATION | doi:10.20944/preprints202003.0350.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: COVID-19; SARS-CoV-2; coronavirus; novel coronavirus; department policy; radiation oncology
Online: 23 March 2020 (09:55:24 CET)
The COVID-19 pandemic is placing unprecedented stress on healthcare systems around the world. Although Radiation Oncology Departments are not at the frontline of fighting this infectious disease, it is important to implement COVID-19 policies to reduce risk of staff and patient exposure, and to limit the risk of department shutdown or downtime. This brief report describes the policy implemented at George Washington University Radiation Oncology to manage the risks of COVID-19. This includes a General Statement related to the priorities of the Radiation Oncology department, a screening procedure for new and follow-up patients, management policies for critical and non-critical patients with COVID-19 or under quarantine, a policy for the management of patients currently under treatment who are diagnosed or placed in quarantine, a clinical escalation action plan, guidelines for staff meetings and travel, and procedure management. This policy was implemented at George Washington University Radiation Oncology after the first case of COVID-19 was reported in Washington DC on March 7, 2020.
ARTICLE | doi:10.20944/preprints202003.0349.v1
Subject: Life Sciences, Biotechnology Keywords: novel coronavirus; COVID-19; protease; molecular docking; drug designing; ADME; drug repurposing
Online: 23 March 2020 (09:47:49 CET)
The Novel Coronavirus (COVID-19) is a positive-sense single-stranded RNA ((+)ssRNA) virus. The COVID-19 Main Proteases play very important role in the propagation of the Novel Coronavirus (COVID-19). It has already killed more than 8000 people around the world and thousands of people are getting infected every day. Therefore, it is very important to identify a potential inhibitor against COVID-19 Main Proteases to inhibit the propagation of the Novel Coronavirus (COVID-19). We have applied a drug repurposing approach of computational methodology, depending on the synergy of molecular docking and virtual screening techniques, aimed to identify possible potent inhibitors against Novel Coronavirus (COVID-19) from FDA approved antiviral compounds and from the library of active phytochemicals. On the basis of recently resolved COVID-19 Main Protease crystal structure (PDB:6LU7), the library of 100 FDA approved antiviral compounds and 1000 active components of Indian Medicinal Plants extracted for screening against COVID-19 Main Protease. The compounds were further screened using Pyrex virtual screening tool and then best inhibitors, top 19 compounds optimally docked to the COVID-19 Main Protease structure to understand the participation of specific amino acids with inhibitors at active sites. Total 19 best compounds were identified after screening based on their highest binding affinity with respect to the other screened compounds. Out of 19, 6 best compounds were further screened based on their binding affinity and best ADME properties. Nelfinavir exhibited highest binding energy -8.4 kcal/mol and strong stability with the TRP207, ILE281, LEU282, PHE3, PHE291, GLN127, ARG4, GLY283, GLU288, LYS5, LYS137, TYR126, GLY138, TYR126, SER139 and VAL135 amino acid residues of COVID-19 Main Protease participating in the interaction at the binding pocket. In addition to Nelfinavir (-8.4), Rhein (-8.1), Withanolide D (-7.8), Withaferin A (-7.7), Enoxacin (-7.4), and Aloe-emodin (-7.4) also showed good binding affinity and best ADME properties. Our findings suggest that these compounds can be used as potential inhibitors against COVID-19 Main Protease, which could be helpful in inhibiting the propagation of the Novel Coronavirus (COVID-19). Moreover, further in vitro and in vivo validation of these findings would be very helpful to bring these inhibitors to next level study.
ARTICLE | doi:10.20944/preprints202206.0321.v1
Subject: Chemistry, Food Chemistry Keywords: coffee leaf tea; novel food; coffee by-products; Coffea arabica; caffeine; epigallocatechin gallate
Online: 23 June 2022 (09:22:46 CEST)
The production of coffee leaf tea (Coffea arabica) in El Salvador and the influences of processing steps on non-volatile compounds and volatile aroma-active compounds were investigated. The tea was produced according to process steps of conventional tea (Camellia sinensis) with available possibilities on the farm. Influencing factors were the leaf type (old, young, yellow, shoots), processing (blending, cutting, rolling, freezing, steaming), drying (sun drying, oven drying, roasting) and fermentation (wild, yeast, Lactobacillus). Subsequently, the samples were analysed for the maximum levels of caffeine, chlorogenic acid, and epigallocatechin gallate permitted by the European Commission. The caffeine content varied between 0.37 g/100 g dry mass (DM) and 1.33 g/100 g DM, the chlorogenic acid between not detectable and 9.35 g /100 g DM and epigallocatechin gallate could not be detected at all. Furthermore, water content, essential oil, ash content, total polyphenols, total catechins, organic acids, and trigonelline were determined. Gas chromatography—mass spectrometry-olfactometry and calculating of the odour activity values (OAVs) were carried out to determine the main aroma-active compounds, which are β-ionone (honey-like, OAV 132-927), decanal (citrus-like, floral, OAV 14-301), α-ionone (floral, OAV 30-100), (E,Z)-2,6-nonadienal (cucumber-like, OAV 18-256), 2,4-nonadienal (melon-like, OAV 2-18), octanal (fruity, OAV 7-23), (E)-2 nonenal (citrus-like, OAV 1-11), hexanal (grassy, OAV 1-10), and 4-heptenal (green, OAV 1-9).
ARTICLE | doi:10.20944/preprints202201.0466.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: FOXC1; in vitro studies; novel variant; ophthalmic genetics; intrafamilial variability; anterior segment dysgenesis
Online: 31 January 2022 (13:36:18 CET)
Anterior segment dysgenesis (ASD) encompasses a wide spectrum of developmental abnormalities of the anterior ocular segment, including congenital cataract, iris hypoplasia, aniridia, iridocorneal synechiae, as well as Peters, Axenfeld, and Rieger anomalies. Here, we report a large five-generation Caucasian family exhibiting atypical syndromic ASD segregating with a novel truncating variant of FOXC1. The family history is consistent with highly variable autosomal dominant symptoms including isolated glaucoma, iris hypoplasia, aniridia, cataract, hypothyroidism, congenital heart anomalies, and cystic kidney disease. Whole exome sequencing revealed a novel variant [c.313_314insA; p.(Tyr105*)] in FOXC1 that disrupts the alpha-helical region of the DNA-binding forkhead box domain. In vitro studies using a heterologous cell system revealed aberrant cytoplasmic localization of FOXC1 harboring the Tyr105* variant, likely precluding downstream transcription function. Meta-analysis of the literature highlighted the intrafamilial variability related to FOXC1 truncating alleles. This study highlights the clinical variability in ASD and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.
REVIEW | doi:10.20944/preprints202104.0175.v1
Subject: Life Sciences, Biochemistry Keywords: Gut microbiome; Western and indigenous/traditional cultures; gut health; disease; lifestyle; novel microbials
Online: 6 April 2021 (12:40:04 CEST)
The mammalian gut ecosystem plays critical roles in multiple functions related to health and homeostasis. In many cases, disturbances in the gut ecosystem are associated with a large number of metabolic and chronic diseases and disorders such as diabetes, cancer, and obesity. A diverse community of microorganisms ranging from viruses to bacteria comprise the gut microbiota, which is often considered as an organ in itself. Recent studies have profiled the influence of lifestyles and dietary behavior by comparing the gut microbiome of populations with different cultural underpinnings. In this review, we provide an overview of the studies which report the influence on the gut microbial composition of dietary and lifestyle patterns in different contexts such as western industrialized countries and indigenous cultures (corresponding to different lifestyle gradients such as hunter-gatherers and pastoralists) and how this association may influence health and disease.
REVIEW | doi:10.20944/preprints202104.0008.v1
Subject: Medicine & Pharmacology, Allergology Keywords: micronutrients supplementation; micronutrients deficiency; prevention and treatment; novel coronavirus; COVID-19; SARS; MERS
Online: 1 April 2021 (10:21:32 CEST)
Background: Micronutrients has roles in strengthening and maintaining immune function, but its supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. Methods: Systematic literature searches conducted in 5 electronic databases identified 751 unique studies, of which 33 studies (5 supplementation studies, 1 supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. Findings: A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures – mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. Conclusion: The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.
REVIEW | doi:10.20944/preprints202009.0552.v1
Subject: Biology, Entomology Keywords: Malaria; Amazon; Brazil; Anopheles darlingi; Plasmodium; Control; Challenges; Strategies; Conventional; Novel; Vector; Mosquito
Online: 23 September 2020 (15:26:43 CEST)
In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been achieved towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, these new vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put on research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the development of such innovative tools.
Subject: Keywords: Mathematical model; Novel coronavirus -19; Nonstandard finite difference scheme; Emigration rate. 1. Introduction
Online: 9 May 2020 (11:25:34 CEST)
In this research work, we present a mathematical model for novel coronavirus -19 (NCOVID-19) which is consisted on three different compartments susceptible, infected and recovered classes abbreviated as under convex incident rate involving and emigration rate. We first derive the formulation of the model. Also, we give some qualitative aspects for the model including existence of equilibriums and its stability results by using various tools of nonlinear analysis. Then by mean of nonstandard finite difference scheme (NSFD), we simulate the results against the data of Wuhan city for the sixty days. By means of simulation, we show how protection, exposure, emigration, death and cure rates affect the susceptible, infected and recovered population with the passage of time involving emigration. On the basis of simulation, we observe the dynamical behavior due to emigration of susceptible and infected classes or one of these two.
ARTICLE | doi:10.20944/preprints202003.0444.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: COVID-19; SARS-CoV-2; coronavirus; novel coronavirus; 3D printing; N95; respirator; mask
Online: 31 March 2020 (04:44:06 CEST)
The 2019 Novel Coronavirus (COVID-19) has caused an acute reduction in world supplies of personal protective equipment (PPE) due to increased demand. To combat the impending shortage of equipment including N95 masks, the George Washington University Hospital (GWUH) developed a 3D printed reusable N95 comparable respirator that can be used with multiple filtration units. We evaluated several candidate prototype respirator models, 3D printer filaments, and filtration units detailed here. Our most recent working model was based on a respirator found on an open source maker website and was developed with PLA (printer filament), a removable cap, a removable filtration unit consisting of two layers of MERV 16 sandwiched between MERV 13, and removable elastic bands to secure the mask. Our candidate mask passed our own suction test protocol to evaluate leakage and passed a qualitative Bitrix N95 fit test at employee health at GWUH. Further efforts are directed at improving the current model for seal against face, comfort, and sizing. The 3D model is available upon request and in the supplement of this paper. We welcome collaboration with other institutions and suggest other facilities consider mask fit for their own population when exploring this concept.
ARTICLE | doi:10.20944/preprints202201.0286.v3
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: novel ncRNAs; DE landscape; LSCs and LTCs; LncRNA; MiRNA; CircRNA; ceRNA networks; molecular mechanism
Online: 4 August 2022 (16:29:49 CEST)
ALDH+ H1975 lung adenocarcinoma stem cells (LSCs) are a rare cell population identified in lung adenocarcinoma (LUAD). LSCs can self-renew, drive tumor initiation, growth, metastasis, and recurrence, and are also the predominant cause of poor prognosis due to their intrinsic resistance to drugs and chemotherapy. Consequently, LSCs are a promising target for LUAD therapy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), exert many significant regulatory functions in the pathogenesis of human cancers, showing the necessity for a comprehensive understanding of the mechanisms that underlie lung carcinogenesis. Nonetheless, research on many known transcripts and messenger RNAs (mRNAs) has already generated new information. Unknown biomarkers in ncRNAs and systematic and comprehensive interrelation with unknown ncRNAs and mRNAs may provide further insights into the biology of LUAD. Herein, a set of novel ncRNAs that include miRNAs, lncRNAs, circRNAs, were identified and differentially expressed patterns of ncRNAs and mRNAs in LSCs and ALDH- H1975 LUAD tumor cells (LTCs) were obtained using stringent bioinformatics pipelines. Through a meta-analysis of the identified landscapes, novel competitive endogenous RNA (ceRNA) networks were constructed to reveal the potential molecular mechanisms that regulate the hallmarks of LSCs and LTCs. This study presents a summary of novel ncRNAs and the fundamental roles of differentially expressed ncRNAs implicated in the activity of LSCs and LTCs. In addition, the study also provides a comprehensive resource for the future identification of diagnostic, therapeutic, and prognostic biomarkers in LUAD.
HYPOTHESIS | doi:10.20944/preprints202004.0349.v1
Subject: Keywords: Novel Coronavirus; respiratory distress; Favipiravir; statistics; correlation; beta thalassemia; immunisation; Italy; Sardinia; regression; heme
Online: 19 April 2020 (13:48:56 CEST)
The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent pre-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta- chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research .
ARTICLE | doi:10.20944/preprints202002.0071.v1
Subject: Life Sciences, Virology Keywords: 2019-nCoV; novel corona virus; Wuhan virus; drug; vaccine; spike protein; epitope; vaccine design
Online: 5 February 2020 (15:34:15 CET)
The recent outbreak of the new virus in Wuhan city, China from the sea food market has led to the identification of a new strain called the corona virus and named as novel corona virus (2019-nCoV) belonging to Coronaviridae family. This has created major havoc and concern due to the mortality of 250 persons and affecting more than 10,000 people. This virus causes sudden fever, pneumonia and also kidney failure. In this study a computational approach is proposed for drug and vaccine design. The spike protein sequences were collected from a protein database and analysed with various bioinformatics tools to identify suitable natural inhibitors for the N-terminal receptor binding domain of spike protein. Also, it is attempted to identify suitable vaccine candidates by identifying B-Cell and T-cell epitopes. In the drug design, the tanshinone Iia and methyl Tanshinonate were identified as natural inhibitors based on the docking score. In the vaccine design, B-cell epitope VLLPLVSSQCVNLTTRTQLPPAYTN was found to have the highest antigenicity. FVFLVLLPL of MHC class-I allele and FVFLVLLPL of MHC class-II allele were identified as best peptides based on a number of alleles and antigencity scores. The present study identifies natural inhibitors and putative antigenic epitopes which may be useful as effective drug and vaccine candidates for the eradication of novel corona virus.
ARTICLE | doi:10.20944/preprints201808.0056.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: heat-related illness; international classification; heat cramp; syncope; heat exhaustion; heat stroke; novel classification
Online: 3 August 2018 (03:51:27 CEST)
The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between June 1 and September 30, 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as stage III were significantly higher than those of patients classified as stage I or II. There were no deaths among the patients classified as stage I. This novel classification may avoid underestimating the severity of heat-related illness.
REVIEW | doi:10.20944/preprints201806.0382.v1
Subject: Engineering, Energy & Fuel Technology Keywords: environmental assessment; novel LCEA model; electricity generating supply systems; lifecycle greenhouse gas grid emission factor
Online: 25 June 2018 (11:03:05 CEST)
Environmental assessment is a concept that has been designed to facilitate the present generation to meet their needs without compromising the ability of future generations to meet their own needs as well. Thus, this concept has drawn significant attention from various scholars, researchers and industrial practitioners around the world over the past three decades. Life Cycle Environmental Assessment (LCEA) is a widely metric used to assess the potential ecological impacts, which can be caused by electricity generating supply systems or by other systems than power production plants. However, the current LCEA model is biased and ineffective. Because, its omits factors that are increasingly contributing to the ecological degradation. This study has identified the omitted factors through a critical analysis of a set of previous journal articles conducted in the energy sector. In light of this, this study has developed a novel LCEA framework addressing those blind spots. The framework developed in this study is holistic in nature including all the life cycle stages of a power supply system such as Extraction of the Raw Material (ERM), Transport of Raw Material (TRM), Conversion of Raw into Electricity (CRE), and Transmission and Distribution of Electricity (TDE) to the end users. The novel developed LCEA model has been tested and applied to nine power generation plants such as coal, gas, nuclear, biomass, geothermal, hydro, solar thermal, wind onshore and wind offshore. The results have demonstrated that of conventional technologies including coal, gas, and nuclear, coal energy generating source has got the highest life cycle greenhouse gas Grid Emission Factor (GEF) of 2866 kg CO2e/MWh, followed by gas with 728 kg CO2e/MWh, and nuclear has got the least GEF of 35 kg CO2e/MWh. Whereas of renewable energy sources biomass has got the highest GEF of 1508 kg CO2e/MWh, followed by solar thermal with 46.6 kg CO2e/MWh, hydro 39 kg CO2e/MWh, wind offshore 25.25 kg CO2e/MWh, wind onshore 10.1 kg CO2e/MWh, and geothermal closes the ranking with 6.23 kg CO2e/MWh.
ARTICLE | doi:10.20944/preprints202005.0279.v1
Subject: Social Sciences, Finance Keywords: novel coronavirus; COVID-19; SARS-CoV-2; pandemic; Chinese stock market; Exponential Generalized Autoregressive Conditional Heteroscedasticity
Online: 17 May 2020 (03:11:38 CEST)
This paper aims to quantify the effect of the deadly novel coronavirus (COVID-19) pandemic outbreak on Chinese stock market performance. Shanghai Stock Exchange Composite Index and its component sector indices are examined in this study. The pandemic is represented by a lockdown dummy, new COVID-19 cases and a dummy for 3 February 2020. First, descriptive analysis is performed on these indices to compare their performances before and during the lockdown period. Next, regression analysis with Exponential Generalized Autoregressive Conditional Heteroscedasticity specification is estimated to quantify the pandemic effect on the Chinese stock market. This paper finds that health care, information technology and telecommunication services sectors were relatively more pandemic-resistant, while other sectors were more severely hurt by the pandemic outbreak. The extent to which each sector was affected by pandemic and sentiments in other financial and commodity markets were reported in details in this paper. The findings of this paper are resourceful for investors to avoid huge loss amid pandemic outburst and the China Securities Regulatory Commission in handling future pandemic occurrence to cool down excessive market sentiments.
ARTICLE | doi:10.20944/preprints202105.0546.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: triple negative breast cancer; Pembrolizumab; Atezolizumab; chemotherapy; anti-PD-L1; biomarkers; targeted therapies; development of novel drugs
Online: 24 May 2021 (09:23:50 CEST)
Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: COVID-19; 2019 novel coronavirus; SARS-CoV-2; Deep Transfer Learning; Convolutional Neural Network; Machine Learning; CGAN
Online: 5 May 2020 (04:14:58 CEST)
The coronavirus disease 2019 (COVID-19) is the fastest transmittable virus caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The detection of COVID-19 using artificial intelligence techniques and especially deep learning will help to detect this virus in early stages which will reflect in increasing the opportunities of fast recovery of patients worldwide. This will lead to release the pressure off the healthcare system around the world. In this research, classical data augmentation techniques along with CGAN based on a deep transfer learning model for COVID-19 detection in chest CT scan images will be presented. The limited benchmark datasets for covid-19 especially in chest CT images is the main motivation of this research. The main idea is to collect all the possible images for covid-19 that exists until the very writing of this research and use the classical data augmentations along with CGAN to generate more images to help in the detection of the COVID-19. In this study, five different deep convolutional neural network-based models (AlexNet, VGGNet16, VGGNet19, GoogleNet, and ResNet50) have been selected for the investigation to detect the coronavirus infected patient using chest CT radiographs digital images. The classical data augmentations along with CGAN improve the performance of classification in all selected deep transfer models. The Outcomes show that ResNet50 is the most appropriate deep learning model to detect the COVID-19 from limited chest CT dataset using the classical data augmentation with testing accuracy of 82.91%.
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: 2019 novel coronavirus; COVID-19; SARS-CoV-2; Deep Transfer Learning; Convolutional Neural Network; Machine Learning; GAN
Online: 7 April 2020 (10:59:04 CEST)
The coronavirus (covid-19) pandemic is putting healthcare systems across the world under unprecedented and increasing pressure according to the World Health Organization (WHO). With the advances in computer algorithms and especially Artificial Intelligence, the detection of this type of virus in the early stages will help in fast recovery and help in releasing the pressure off healthcare systems. In this paper, a GAN with deep transfer learning for coronavirus detection in chest x-ray images is presented. The lack of benchmark datasets for covid-19 especially in chest x-rays images is the main motivation of this research. The main idea is to collect all the possible images for covid-19 that exists until the writing of this research and use the GAN network to generate more images to help in the detection of the virus from the available x-rays images with the highest accuracy possible. The dataset used in this research was collected from different sources and it is available for researchers to download and use it. The number of images in the collected dataset is 307 images for four different types of classes. The classes are the covid-19, normal, pneumonia bacterial, and pneumonia virus. The dataset is divided into 90% for the GAN and the training and the validation phase, while 10% used in the testing phase. The GAN helps in generating more images from the original dataset to be 30 times larger than the originally collected dataset. The GAN also help in overcoming the overfitting problem and made the proposed model more robust. Three deep transfer models are selected in this research for investigation. The models are the Alexnet, Googlenet, and Restnet18. Those models are selected based on their small number of layers on their architectures, which will reflect in reducing the complexity of the models and the consumed memory and time. Using a combination of GAN and deep transfer models prove it is efficiency according to validation, testing accuracy, and performance measurements such as precision, recall, and F1 score. Three case scenarios are tested through the paper, the first scenario which includes 4 classes from the dataset, while the second scenario includes 3 classes and the third scenario includes 2 classes. All the scenarios include the covid-19 class as it is the main target of this research to be detected. In the first scenario, the Googlenet is selected to be the main deep transfer model as it achieves 80.6% in testing accuracy. In the second scenario, the Alexnet is selected to be the main deep transfer model as it achieves 85.2% in testing accuracy, while in the third scenario which includes 2 classes(covid-19, and normal), Googlenet is selected to be the main deep transfer model as it achieves 100% in testing accuracy and 99.9% in the validation accuracy. All the performance measurement strengthen the obtained results through the research. Finally, this research may be considered one of the first trails to use GAN and deep transfer models together to help in detecting coronaviruses (covid-19) within the absence of a benchmark dataset around the world, especially in x-rays chest images.
ARTICLE | doi:10.20944/preprints202003.0440.v1
Subject: Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; 2019-nCoV; novel corona virus; drug repurposing; chloroquine; high-risk group; asymptomatic
Online: 30 March 2020 (07:24:16 CEST)
COVID-19 (2019-nCoV) is a pandemic disease with an estimated mortality rate of 3.4% (estimated by the WHO as of March 3, 2020). Until now there is no antiviral drug and vaccine for COVID-19. The current overwhelming situation by COVID-19 patients in hospitals is likely to increase in the next few months. About 15 percent of patients with serious disease in COVID-19 require immediate health services. Rather than waiting for new anti-viral drugs or vaccines that take a few months to years to develop and test, several researchers and public health agencies are attempting to repurpose medicines that are already approved for another similar disease and have proved to be fairly effective. This study aims to identify FDA approved drugs that can be used for drug repurposing and identify biomarkers among high- risk and asymptomatic groups. In this study gene-disease association related to COVID-19 reported mild, severe symptoms and clinical outcomes were determined. The high-risk group was studied related to SARS-CoV-2 viral entry and life cycle by using Disgenet and compared with curated COVID-19 gene data sets from the CTD database. The overlapped gene sets were enriched and the selected genes were constructed for protein-protein interaction networks. Through interactome, key genes were identified for COVID-19 and also for high risk and asymptomatic groups. The key hub genes involved in COVID-19 were VEGFA, TNF, IL-6, CXCL8, IL10, CCL2, IL1B, TLR4, ICAM1, MMP9. The identified key genes were used for drug-gene interaction for drug repurposing. The chloroquine, lenalidomide, pentoxifylline, thalidome, sorafenib, pacitaxel, rapamycin, cortisol, statins were proposed to be probable drug repurposing candidates for the treatment of COVID-19. However, these predicted drug candidates need to be validated through randomized clinical trials. Also, a key gene involved in high risk and the asymptomatic group were identified, which can be used as probable biomarkers for early identification.
Subject: Biology, Ecology Keywords: non-native populations; geographic expansion; invasiveness; invasibility; dispersal; phenotypic plasticity; evolution; historical ecosystem; hybrid ecosystem; novel ecosystem
Online: 30 October 2019 (07:13:34 CET)
Biological invasions have reached an unprecedented level and the number of introduced species is still increasing worldwide. Despite major advances in invasion science, the determinants of success of introduced species, the magnitude and dimensions of their impact, and the mechanisms sustaining successful invasions are still debated. Empirical studies show divergent impacts of non-native populations on ecosystems and contrasting effects of biotic and abiotic factors on the dynamics of non-native populations; this is hindering the emergence of a unified theory of biological invasions. We propose a synthesis that merges perspectives from population, community, and ecosystem levels. Along a timeline of ecosystem transformation driven by non-native species, from historical to human-modified ecosystems, we order invasion concepts and theories to clarify their chaining and relevance during each step of the invasion process. This temporal sorting of invasion concepts shows that each concept is relevant at a specific stage of the invasion. Concepts and empirical findings on non-native species may appear contradictory. However, we suggest that, when mapped onto an invasion timeline, they may be combined in a complementary way. An overall scheme is proposed to summarise the theoretical dynamics of ecosystems subjected to invasions. For any given case study, this framework provides a guide through the maze of theories and should help choose the appropriate concepts according to the stage of invasion.
ARTICLE | doi:10.20944/preprints201909.0220.v1
Subject: Biology, Plant Sciences Keywords: novel cytorhabdovirus; high-throughput sequencing; aphid transmission; mechanical inoculation; grafting-mediated virus transmission; fragaria spp.; chaetosiphon fragaefolii
Online: 19 September 2019 (11:17:42 CEST)
Virus diseases of strawberry present several complex problems. More than 25 viruses have been described in the genus Fragaria thus far. Here, we describe a novel rhabdovirus, tentatively named strawberry virus 1 (StrV-1), that infects F. ananassa and F. vesca plants. Genomic sequences of three distinct StrV-1 genotypes co-infecting a single F. ananassa host were obtained using combined Illumina and Ion Proton high-throughput sequencing. StrV-1 was transmitted to herbaceous plants via Aphis fabae and A. ruborum, further mechanically transmitted to Nicotiana occidentalis 37B and sub-transferred to N. benthamiana, N. benthamiana DCL2/4i, N. occidentalis 37B and Physalis floridana plants. Irregular chlorotic sectors on leaf blades and the multiplication of calyx leaves seem to be the diagnostic symptoms for StrV-1 on indexed F. vesca clones. StrV-1 was detected in asymptomatic grafted plants and in 49 out of 159 field strawberry samples via RT-PCR followed by Sanger sequencing. The bacilliform shape of the virions, which have a cytoplasm-limited distribution, their size, and phylogenetic relationships support the assignment of StrV-1 to a distinct species of the genus Cytorhabdovirus. Acyrthosiphon malvae, A. fabae and A. ruborum were shown to transmit StrV-1 under experimental conditions.
REVIEW | doi:10.20944/preprints202004.0540.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: cholinergic anti-inflammatory pathway; novel coronavirus; SARS-CoV-2; COVID-19; meta-analysis; Cytokine Release Syndrome; nicotine; smokers
Online: 30 April 2020 (17:01:38 CEST)
SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It produces severe acute respiratory disease (COVID-19), which is fatal in many cases, characterised by cytokine release syndrome (CRS). According to the World Health Organization (WHO), those who smoke are likely to be more vulnerable to infection. Here, in order to clarify the epidemiologic relationship between smoking and COVID-19, we present a systematic literature review until 28 April 2020 and a meta-analysis. It includes 18 recent COVID-19 clinical and epidemiological studies based on smoking patient status from 720 initial studies in China, USA, and Italy. The percentage of hospitalised current smokers was 7.7% (95%CI: 6.9-8.4) in China, 2.3% (95%CI: 1.7-2.9) in the USA and 7.6% (95%CI: 4.2-11.0) in Italy. These percentages were compared to the smoking prevalence of each country and statistically significant differences were found in them all (p <0.0001). By means of the meta-analysis, we offer epidemiological evidence showing that smokers were statistically less likely to be hospitalised (OR=0.18, 95%CI: 0.14-0.23, p<0.01). CRS and exacerbated inflammatory response are associated with aggravation of hospitalise patients. In this scenario, we hypothesise that nicotine, not smoking, could ameliorate the cytokine storm and severe related inflammatory response through the cholinergic-mediated anti-inflammatory pathway.
ARTICLE | doi:10.20944/preprints202004.0543.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: Coronavirus; COVID-19; SARS-CoV-2; Pandemic; Paramedic; Infection prevention and control; Aerosols; Aerosol Generating Procedures; Novel virus; Wellbeing
Online: 30 April 2020 (17:20:55 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes the new Coronavirus disease (COVID-19). The symptoms range from mild to severe with a higher incidence of severe cases seen in patients with risk factors such as older age and comorbidities. COVID-19 is mainly spread through the inhalation of respiratory droplets from coughing or sneezing or via contact with droplet-contaminated surfaces. Paramedics should be aware that some aerosol generating procedures (AGPs) may put them at a higher risk of contracting the virus via possible airborne transmission. The use of remote triage clinical assessment is likely to increase as a result of the pandemic. There is no curative drug treatment for the virus and some medications may exacerbate its effects or make patients more susceptible to it. Paramedics should accept that feeling stressed by the pandemic is a natural response. Official guidelines and advice are evolving continually as the evidence on SARS-CoV-2 and COVID-19 grows. Paramedics should keep up to date with the latest clinical guidance from their employers.
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; novel severe acute respiratory syndrome coronavirus 2; ancestral reconstruction; clonality; source of entry; dispersal routes
Online: 28 June 2020 (09:21:49 CEST)
The coronavirus disease 2019 (COVID-19) was officially declared a pandemic on the 11th March 2020. It is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), impacting the lower respiratory tract. International travel to Australia during the early stages of the pandemic prior to border closure provided avenues for this virus to spread into Australia. There is little understanding of the clonality of SARS-CoV-2 isolates in Australia, and where they originated. This study aimed to investigate the clonality and ancestral sources of SARS-CoV-2 isolates in Australia using in silico methods. We retrieved 1,346 complete genomes from Australia along with 153 genomes from other countries from the NCBI nucleotide database and Global Initiative On Sharing All Influenza Data (GISAID). We then constructed a representative population of 270 sequences for downstream phylogenetic analysis and ancestral area reconstruction. Overall, two major clusters, one stemming from Europe and another from Asia, especially East Asia, were observed, implying at least two major transmission events with subsequent clades confirming the multiclonality of Australian isolates. We also identified three potential dissemination routes of SARS-CoV-2 into Australia. This study supports the hypothesis of multiple clonality and dispersals of SARS-CoV-2 isolates into Australia.
REVIEW | doi:10.20944/preprints202103.0490.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Covid-19; Long Covid-19; Long Haulers Covid; Post Covid-19 Syndrome; Post-Acute Covid-19; Corona Virus; SARS-Cov-2; Novel Corona Virus 2019; Post-Acute SARS-CoV-2; PASC, Post-Acute Sequelae of COVID-19; Late Sequelae COVID-19
Online: 18 March 2021 (17:16:52 CET)
Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.
ARTICLE | doi:10.20944/preprints202006.0165.v2
Subject: Life Sciences, Virology Keywords: Conserved signature indels (CSIs) specific for SARS and SARS-CoV-2-related viruses. Molecular markers distinguishing different clades of Sarbecovirus, Evolutionary relationships between SARS and SARS-CoV-2-related viruses, Origin of SARS-CoV-2 and Pangolin CoV_MP789 viruses, Novel sequence and structural features of spike and nucleocapsid proteins. Genetic recombination.
Online: 26 August 2020 (10:17:16 CEST)
Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.
ARTICLE | doi:10.20944/preprints201802.0163.v1
Subject: Physical Sciences, Optics Keywords: optical metamaterials; fundamental concepts in photonics; light-matter interactions at the subwavelength and nanoscale; fundamental understanding of linear and nonlinear optical processes in novel metamaterials underpinning photonic devices and components; advancing the frontier of nanophotonics with the associated nanoscience and nanotechnology; nanostructures that can serve as building blocks for nano-optical systems; use of nanotechnology in photonics; nonlinear nanophotonics, plasmonics and excitonics; subwavelength components and negative index materials; slowing, store, and processing light pulses; materials with such capabilities that could be used for optical sensing, tunable optical delay lines, optical buffers, high extinction optical switches, novel image processing hardware, and highly-efficient wavelength converters
Online: 26 February 2018 (11:24:39 CET)
Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.