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.
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.
REVIEW | doi:10.20944/preprints201710.0185.v3
Subject: Life Sciences, Biochemistry Keywords: epigenome; DNA modification; cytosine methylation; gene regulation; histone modification; 5-methylcytosine; stress response
Online: 25 December 2017 (09:43:03 CET)
Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.
ARTICLE | doi:10.20944/preprints202012.0710.v1
Subject: Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; D614G; N501Y; S477N; mink; VOC 202012/01; B.1.1.7
Online: 28 December 2020 (17:00:23 CET)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an outbreak of COVID-19 disease in humans with the aid of spike protein. It consists of a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2). The aim of this study was to examine the mutational effect of spike protein on the sequence through an interaction study of the mutant spike protein and the human ACE2 protein at the structural level. A total of 17,227 spike proteins from Asia, Africa, Europe, Oceania, South America, and North America were compared to the Wuhan spike protein reference sequence (Wuhan-Hu-1). The structural and stability implications of D614G, N501Y, and S477N mutations were evaluated. The binding affinity between mutated RBD and human ACE2 protein was also studied. The D614G mutation may have originated in Germany, Europe based on the date of the first sample collection report. It is now widely circulated all over the world with most occurrences in North America. The mutations N501Y and S477N may have originated from Oceania based on the date of the first sample collection report and also have the highest occurrences in Oceania. Based on the computational analysis of mutational effects, the D614G, N501Y, and S477N mutations decreased stability and were tolerated. For disease propensity prediction, N501Y was more prone to disease compared to D614G, while S477N was not prone to disease. The mutation of D to G at position 614 and S to N at position 477 for secondary structure prediction shows no changes in secondary structure while remaining in the coil region, whereas the mutation of N to Y at position 501 changes from coil structure to extended strand. N501Y mutation has a higher affinity to human ACE2 protein compared to D614G and S477N based on a docking study. D614G spike mutation was identified to exist between the two hosts based on a comparison of SARS-CoV-2 derived between the mink and human. Further research is needed on the link between the mink mutation N501T and the mutation N501Y in humans, which has evolved as a separate variant.
Subject: Social Sciences, Accounting Keywords: Climate change risk; carbon dioxide; asset pricing modeling
Online: 12 July 2021 (12:01:49 CEST)
In this study, I extend the Fama and French five-factor asset pricing model with a sixth factor, namely, carbon risk, to investigate its impact on equity returns. To measure carbon risk, a new factor ‘pollutant minus green,’ is developed using the difference between the weighted average returns of pollutant and green firms across 51 developed and emerging countries across four categories—North America, Europe, Emerging Markets, and the Asia Pacific. The results reveal that North America, Europe, and Asia Pacific markets have a carbon risk premium that gets eliminated in small-cap firms. The carbon risk factor is further tested in left-hand side (LHS) test asset portfolios and found to be more pronounced with size-effect anomaly; specifically, small stock firms report greater declining average returns because of more exposure than the mega-cap stocks to carbon dioxide emissions. Furthermore, size-effect anomaly prevails with profitability and investment factors across firms. Therefore, high profitability, as well as high investment small firms, show a greater decline than the big stock firms in average returns when their carbon dioxide emissions increase. The asset pricing model evaluation is carried out through the Gibbons, Ross, and Shanken test. The six-factor model directed at capturing carbon risk patterns in average equity returns performs better than the three-factor and five-factor models of Fama and French (1993 and 2015) in the majority of categories under 3x3 sorting and compete with both Fama and French model under 2x4x4 sorted LHS portfolios. The finding of this study offers various useful applications for investors, policymakers, brokers, corporations, governmental pollution abatement institutions, and other stakeholders who wish to obtain carbon risk premium.
ARTICLE | doi:10.20944/preprints202009.0012.v1
Online: 1 September 2020 (11:42:14 CEST)
The specificity and potency of venom components gives them a unique advantage in development of various pharmaceutical drugs. Though venom is a cocktail of proteins rarely is the synergy and association between various venom components studied. Understanding the relationship between various components is critical in medical research. Using meta-analysis, we found underlying patterns and associations in the appearance of the toxin families. For Crotalus, Dis has the most associations with the following toxins: PDE; BPP; CRL; CRiSP; LAAO; SVMP P-I & LAAO; SVMP P-III and LAAO. In Sistrurus venom CTL and NGF had most associations. These associations can be used to predict presence of proteins in novel venom and to understand synergies between venom components for enhanced bioactivity. Using this approach, the need to revisit classification of proteins as major components or minor components is highlighted. The revised classification of venom components needs to be based on ubiquity, bioactivity, number of associations and synergies. The revised classification will help in increased research on venom components such as NGF which have high medical importance.
REVIEW | doi:10.20944/preprints202001.0364.v2
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: 2019-nCoV; SARS-CoV; drought; bat; green light
Online: 4 February 2020 (10:31:47 CET)
The new coronavirus (2019-nCoV) in Wuhan has caused virus outbreaks in many provinces and cities in China, and several neighboring countries were also affected. In recent years, coronavirus several outbreaks around the world were reported, however researchers could not predict its onset. Coincidentally, the birthplace of another coronavirus (SARS-CoV) that causes serious public health problems is also in China. This review compares and analyzes the external environment, natural hosts, intermediate hosts, and susceptible populations when these two coronaviruses occurred. Based on the analysis results, we found that the 2019-nCov virus outbreak in Wuhan was not an accidental phenomenon, but a result of a combination of factors. At the same time, through the conclusions of these analyses, we will be able to get a glimpse of the trajectories of new coronaviruses and curb the virus outbreak in future.
REVIEW | doi:10.20944/preprints202105.0020.v1
Subject: Chemistry, Analytical Chemistry Keywords: Ehretia laevis; Pharmacological Activities; Phytochemistry; Traditional Use
Online: 4 May 2021 (13:59:18 CEST)
Ehretia laevis Roxb. (Boraginaceae) has been extensively used as a traditional remedy for the treatment of a diverse range of ailments related to the respiratory system, the gastrointestinal tract, the reproductive system, and against several infections. This review critically assesses and documents, for the ﬁrst time, the fragmented information on E. laevis, including its botanical description, folklore uses, bioactive phytometabolites and pharmacological activities. The goal is to explore this plant therapeutically. Ethnomedicinal surveys reveal that E. laevis has been used by tribal communities in Asian countries for the treatment of various disorders. Quantitative and qualitative phytochemical investigations of E. laevis showed the presence of important phytoconstituents such as pentacyclic triterpenoids, phenolic acids, flavonoids, fatty acids, steroids, alkaloids, aliphatic alcohols, hydrocarbons, amino acids, carbohydrates, vitamins and minerals. Fresh plant parts, crude extracts, fractions and isolated compounds have been reported to exhibit broad spectrum of therapeutic activities viz., antioxidant, antiarthritic, antidiabetic, anti-inflammatory, antiulcer, antidiarrheal, antidysenteric, wound healing and anti-infective activities. E. laevis is shown to be an excellent potential source of drugs for the mitigation of jaundice, asthma, dysentery, ulcers, diarrhea, ringworm, eczema, diabetes, fissure, syphilis, cuts and wounds, inflammation, liver problems, venereal and infectious disorders. Although few investigations authenticated its traditional uses but employed uncharacterized crude extracts of the plant, the major concerns raised are reproducibility of therapeutic efficacy and safety of plant material. The outcomes of limited pharmacological screening and reported bioactive compounds of E. laevis suggest that there is an urgent need for in-depth pharmacological investigations of the plant.
ARTICLE | doi:10.20944/preprints202005.0403.v1
Subject: Earth Sciences, Environmental Sciences Keywords: zoonotic; corona virus; COVID-19; SARS; MERS; global health emergency; India; lockdown strategies
Online: 24 May 2020 (19:34:03 CEST)
Global emerge of zoonotic novel corona virus (COVID-19) became a pandemic and its effect to mankind is talk of the town now a days. This tiny, invisible enemy has affected every country in the world and almost every living directly or indirectly and nationwide complete lockdown has triggered a short-term environmental impact. Since 2003, corona virus came into existence in the form of Severe Acute Respiratory Syndrome (SARS) and more evolved Middle East Respiratory Syndrome (MERS) in 2012. This time, at the end of December 2019, outbreak of novel corona virus COVID-19 (also known as SARS-CoV2, nCoV-2019) draw attention as global health emergency. World Health Organization (WHO) report says that the outbreak of this virus is so immense, it has already affected 35,57,235 people and caused death to 2,45,150 people worldwide and 46,433 Indians got affected with 1568 death as on 5th May 2020 (2:00 am) and these numbers are increasing exponentially day by day. Virologist, micro-biologist and science community are hammering their head very hard to find out cure and vaccine against this powerful virus and to prevent mass demise of mankind. In order to curb the spread of COVID-19, Janta curfew on 22.03.2020 and nationwide complete lockdown was implemented in India for 21 days (phase-I, from 25.03.2020 to 14.04.2020) to stop community transmission of third stage, for 19 days (phase-II, 15.04.2020 to 03.05.2020) and 14 days (phase-III, 04.05.2020 to 17.05.2020) complete lockdown to minimize the community transmission effect. During complete lockdown and quarantine period a drastic change in Earth’s atmosphere, including reduction in emission of greenhouse gases, air pollution (~50% fall in air quality index), noise pollution, water pollution and solid waste pollution, have been recorded by government agencies as well as private agencies. In this paper we considered data of Janta curfew, phase-I and phase-II lockdown to link between geological and environmental aspect related to environmental impact due to emerge of COVID-19 and massive reduction in pollution level during complete lockdown in India. We propose future lockdown strategies to minimize the emission of greenhouse gas by ~100 Mt to ~200Mt (3.33% to 6.66%) of GHGtotal per year by 2-4 days per month nationwide lockdown or ~70 Mt to ~140 Mt (2.33% to 4.66%) of GHGtotal per year by 2-4 days per month complete lockdown of energy sectors only.
ARTICLE | doi:10.20944/preprints202106.0024.v1
Subject: Materials Science, Biomaterials Keywords: AMCs; Optical Microscope; Wear; Friction; Oxide layer; Worn Debris; Tribology; Surface topography; Surface engineering.
Online: 1 June 2021 (11:06:59 CEST)
In this study, an investigation on the influence of In-situ tribo-oxide-layer on non-lubricated tribological behaviours of LM27/SiCp composites was carried out at different applied loads. The variations in wear performance and microstructure of brake lining friction material (LM27) with the addition of different amounts and sizes of SiCp are explored. For this purpose, LM27/SiCp composite materials were manufactured by stir casting route varying the amount of particle reinforced from 3wt.% to 12wt.% with a different size range (fine: 1-20µm and coarse: 106-125µm). Non-lubricated dry wear tests of LM27/SiCp composites samples were trialled at different loads from 9.8N to 49N by using a pin-on-disc machine system. At a contact pressure of 0.2-1 MPa, LM27/SiCp composites with 12wt.% reinforcement showed a lower coefficient of friction than other composites. In-situ formation of oxide layers on the contact region of the specimen supports the self-lubrication during the wear test, which is responsible for better wear performance of LM27/SiCp composites. However, these study portraits that composite with 12wt. % fine size SiCp exhibits better wear performance in comparison to the other developed composites.
ARTICLE | doi:10.20944/preprints202008.0092.v1
Subject: Keywords: COVID-19; SARS-CoV-2; epitopes; B-cell; T-cell; immuno informatics; MHC-I; MHC-II
Online: 4 August 2020 (11:18:27 CEST)
Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.
REVIEW | doi:10.20944/preprints201811.0571.v2
Subject: Life Sciences, Genetics Keywords: prostate cancer; prostate-specific antigen; incidence; genomics; next generation sequencing
Online: 3 April 2019 (10:15:50 CEST)
In the recent past, there has been a rise in Prostate Cancer (PCa) in Asia, particularly India. Although systematic reviews on PCa have dealt on the genetics, genomics and the environmental influence in causal of PCa, no predictive analytics in comparing the PCa from Caucasian, American to Asian population was attempted. In this review article, we have attempted to elaborate this aspect of PCa and deliberated on challenges related to next generation sequencing methods of PCa’s manifestation when compared to the west.