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Preprint ARTICLE | doi:10.20944/preprints202005.0057.v2

Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study

Francisco Javier Membrillo, Germán Ramírez-Olivencia, Miriam Estébanez, Begoña de Dios, María Dolores Herrero, Tatiana Mata, Alberto M. Borobia, Carlos Gutiérrez, María Simón, Ana Ochoa, Yolanda Martínez, Alejandro Aguirre, Francisco de Asís Alcántara, Pablo Fernández-González, Elena López, Paula Valle, Sergio Campos, María Navarro, Lucía Elena Ballester

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; treatment; drug; survival; antiviral; hydroxychloroquine

Online: 9 May 2020 (04:45:37 CEST)

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Preprint REVIEW | doi:10.20944/preprints202403.0881.v1

Concerns regarding Transfusions of Blood Products Derived from Genetic Vaccine Recipients and Proposals for Specific Measures

Jun Ueda, Hideyuki Motohashi, Yuriko Hirai, Kenji Yamamoto, Yasufumi Murakami, Masanori Fukushima, Akinori Fujisawa

Subject: Medicine And Pharmacology, Transplantation Keywords: COVID-19 vaccine; genetic vaccine; blood product; blood transfusion; spike protein; post-vaccination syndrome; harm–benefit assessment; prion; spikeopathy; inspection standard; diagnostic criteria

Online: 15 March 2024 (08:54:06 CET)

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Preprint REVIEW | doi:10.20944/preprints202307.1198.v1

Autopsy Proven Fatal COVID-19 Vaccine-Induced Myocarditis

Nicolas Hulscher, Roger Hodkinson, William Makis, Peter McCullough

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: myocarditis; sudden death; chest pain; autopsy; necropsy; COVID-19; COVID-19 vaccines; mRNA; SARS-CoV-2 vaccination; death; excess mortality; spike protein; organ system

Online: 18 July 2023 (09:34:51 CEST)

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Background: COVID-19 vaccines have been linked to myocarditis which in some circumstances can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. Methods: We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-related myocarditis through July 3^rd, 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included, without imposing any additional restrictions. Causality in each case was determined by three independent reviewers with cardiac pathology experience and expertise. Results: We initially identified 1,691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In 2 cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome (MIS). The mean and median number of days from last COVID-19 vaccination until death was 6.2 and 3 days, respectively. Most of the deaths occurred within a week from the last injection. We established that all 28 deaths were causally linked to COVID-19 vaccination by independent adjudication. Conclusions: The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death from suspected myocarditis in cases where sudden, unexpected death has occurred in a vaccinated person. Urgent investigation is required for the purpose of risk stratification and mitigation in order to reduce the population occurrence of fatal COVID-19 vaccine-induced myocarditis.

Preprint ARTICLE | doi:10.20944/preprints202004.0457.v2

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Anton S.M. Dofferhoff, Ianthe Piscaer, Leon J. Schurgers, Jona Walk, Jody M.W. van den Ouweland, Tilman M. Hackeng, Pim A. de Jong, Reinoud Gosens, Petra Lux, Henny van Daal, Cecile Maassen, Esther G.A. Maassen, Loes E.M. Kistemaker, Cees Vermeer, Emiel F.M. Wouters, Rob Janssen

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Covid-19; desmosine; dp-ucMGP; elastic fibers; factor II; matrix Gla protein; PIVKA-II; protein S; vitamin K; vitamin K antagonist

Online: 29 May 2020 (04:16:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints202303.0140.v1

Autoimmune Inflammatory Reactions Triggered by the COVID-19 Genetic Vaccines in Terminally Differentiated Tissues

Panagis Polykretis, Alberto Donzelli, Janci C. Lindsay, David Wiseman, Anthony M. Kyriakopoulos, Michael Mörz, Paolo Bellavite, Masanori Fukushima, Stephanie Seneff, Peter A. McCullough

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; genetic vaccines; adverse reactions; autoimmunity; immunohistochemistry; spike protein

Online: 8 March 2023 (02:57:33 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202402.1096.v1

Delayed Fatal Pulmonary Hemorrhage Following COVID-19 Vaccination: Case Report, Batch Analysis, And Proposed Autopsy Checklist

Nicolas Hulscher, Peter A. McCullough

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19 vaccination; Death; Autopsy; Pulmonary hemorrhage; Adverse events; Spike protein; Batch; Thrombosis; Safety

Online: 20 February 2024 (06:33:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0061.v1

Deep Learning Based Drug Screening for Novel Coronavirus 2019-nCov

Haiping Zhang, Konda Mani Saravanan, Yang Yang, Md. Tofazzal Hossain, Junxin Li, Xiaohu Ren, Yanjie Wei

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Coronavirus; Deep learning; Drug screening; homology modeling; main protease

Online: 5 February 2020 (10:59:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0047.v1

Possible Inhibitors of ACE2, the Receptor of 2019-nCoV

Qinghua Cui, Chuanbo Huang, Xiangwen Ji, Wanlu Zhang, Fenghong Zhang, Liang Wang

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2019-nCoV; therapeutic strategies; drug; ACE2

Online: 4 February 2020 (10:59:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0360.v2

TMPRSS2 Transcriptional Inhibition as a Therapeutic Strategy for COVID-19

Xinchen Wang, Ryan Dhindsa, Gundula Povysil, Anthony Zoghbi, Joshua Motelow, Joseph Hostyk, Nicholas Nickols, Matthew Rettig, David B. Goldstein

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; transcriptional inhibition; COVID-19; drug repurposing; TMPRSS2

Online: 28 April 2020 (09:39:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0281.v2

Mutation Hot Spots in Spike Protein of SARS-CoV-2 Virus

Feroza Begum, Arup Kumar Banerjee, Upasana Ray

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; S protein; RBD; S1; S2

Online: 7 September 2020 (04:15:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201911.0330.v1

Identifying Early-Warning Signals for the Sudden Transition from Mild to Severe Tobacco Rtch Disease by Dynamical Network Biomarkers

Adrián Tarazona, Javier Forment, Santiago F. Elena

Subject: Biology And Life Sciences, Virology Keywords: complex systems; DNB; phase transitions; plant-virus interaction; Potyvirus; protein-protein interaction networks; response to infection; systems biology; Tobacco etch virus

Online: 27 November 2019 (04:42:28 CET)

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Preprint REVIEW | doi:10.20944/preprints202009.0395.v1

V483a – an Emerging Mutation Hotspot of Sars-Cov-2

Omar Ashwaq, Pratibha Manickavasagam, Sk Manirul Haque

Subject: Biology And Life Sciences, Virology Keywords: Spike protein, V483A, substitution mutation, virus-host cell interaction, high transmission, infectivity.

Online: 17 September 2020 (10:43:02 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0122.v2

Can Melatonin Reduce the Severity of COVID-19 Pandemic?

Alex Shneider, Aleksandr Kudriavtsev, Anna Vakhrusheva

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: melatonin; coronavirus; pandemic; SARS-CoV-2; bat; lung; apoptosis; programmed cell death; mortality; morbidity; COVID-19; drug

Online: 9 April 2020 (09:24:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0349.v1

In Silico Identification of Potent COVID-19 Main Protease Inhibitors from FDA Approved Antiviral Compounds and Active Phytochemicals through Molecular Docking: A Drug Repurposing Approach

Vaishali Chandel, Sibi Raj, Brijesh Rathi, Dhruv Kumar

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: novel coronavirus; COVID-19; protease; molecular docking; drug designing; ADME; drug repurposing

Online: 23 March 2020 (09:47:49 CET)

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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.

Preprint COMMUNICATION | doi:10.20944/preprints202002.0418.v2

Virtual Screening Based Prediction of Potential Drugs for COVID-19

Sekhar Talluri

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: virtual screening; molecular docking; drug repurposing; drug repositioning; anti-viral drugs; Coronavirus; COVID-19; 2019-nCoV; SARS-CoV-2

Online: 9 March 2020 (02:29:04 CET)

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Preprint REVIEW | doi:10.20944/preprints202306.1306.v1

Exploring Therapeutic Applications of Autophagy in Spike Protein-Related Pathology

Matthew Halma, Paul Marik, Yusuf Saleeby

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Fasting; autophagy; long-COVID; post-vaccination syndrome; spike protein; mitochondria; mitophagy

Online: 19 June 2023 (07:39:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0413.v1

Ontological and Bioinformatic Analysis of Anti-Coronavirus Drugs and Their Implication for Drug Repurposing against COVID-19

Yingtong Liu, Wallace K.B. Chan, Zhigang Wang, Junguk Hur, Jiangan Xie, Hong Yu, Yongqun He

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coronavirus; drug; COVID-19; SARS; MERS; ontology; ChEBI; NDF-RT; DrON; bioinformatics

Online: 29 March 2020 (01:58:40 CET)

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Coronavirus-infected diseases have posed great threats to human health. In past years, highly infectious coronavirus-induced diseases, including COVID-19, SARS, and MERS, have resulted in world-wide severe infections. Our literature annotations identified 110 chemical drugs and 26 antibodies effective against at least one human coronavirus infection in vitro or in vivo. Many of these drugs inhibit viral entry to cells and viral replication inside cells or modulate host immune responses. Many antimicrobial drugs, including antimalarial (e.g., chloroquine and mefloquine) and antifungal (e.g., terconazole and rapamycin) drugs as well as antibiotics (e.g., teicoplanin and azithromycin) were associated with anti-coronavirus activity. A few drugs, including remdesivir, chloroquine, favipiravir, and tocilizumab, have already been reported to be effective against SARS-CoV-2 infection in vitro or in vivo. After mapping our identified drugs to three ontologies ChEBI, NDF-RT, and DrON, many features such as roles and mechanisms of action (MoAs) of these drugs were identified and categorized. For example, out of 57 drugs with MoA annotations in NDF-RT, 47 have MoAs of different types of inhibitors and antagonists. A total of 29 anticoronaviral drugs are anticancer drugs with the antineoplastic role. Two clustering analyses, one based on ChEBI-based semantic similarity, the other based on drug chemical similarity, were performed to cluster 110 drugs to new categories. Moreover, differences in physicochemical properties among the drugs were found between those inhibiting viral entry and viral replication. A total of 163 host genes were identified as the known targets of 68 anti-coronavirus drugs, resulting in a network of 428 interactions among these drugs and targets. Chlorpromazine, dasatinib, and anisomycin are the hubs of the drug-target network with the highest number of connected target proteins. Many enriched pathways such as calcium signaling and neuroactive ligand-receptor interaction pathways were identified. These findings may be used to facilitate drug repurposing against COVID-19.

Preprint ARTICLE | doi:10.20944/preprints202003.0440.v1

COVID-19: A Drug Repurposing and Biomarker Identification by Using Comprehensive Gene-Disease Associations through Protein-Protein Interaction Network Analysis

Suresh Kumar

Subject: Biology And 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)

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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.

Preprint REVIEW | doi:10.20944/preprints202005.0376.v1

Computational Strategies to Combat COVID-19: Useful Tools to Accelerate SARS-CoV-2 and Coronavirus Research

Franziska Hufsky, Kevin Lamkiewicz, Alexandre Almeida, Abdel Aouacheria, Cecilia Arighi, Alex Bateman, Jan Baumbach, Niko Beerenwinkel, Christian Brandt, Marco Cacciabue, Sara Chuguransky, Oliver Drechsel, Robert D. Finn, Adrian Fritz, Stephan Fuchs, Georges Hattab, Anne-Christin Hauschild, Dominik Heider, Marie Hoffmann, Martin Hölzer, Stefan Hoops, Lars Kaderali, Ioanna Kalvari, Max von Kleist, René Kmiecinski, Denise Kühnert, Gorka Lasso, Pieter Libin, Markus List, Hannah F. Löchel, Maria J. Martin, Roman Martin, Julian Matschinske, Alice C. McHardy, Pedro Mendes, Jaina Mistry, Vincent Navratil, Eric Nawrocki, Áine Niamh O'Toole, Nancy Palacios-Ontiveros, Anton I. Petrov, Guillermo Rangel-Piñeros, Nicole Redaschi, Susanne Reimering, Knut Reinert, Alejandro Reyes, Lorna Richardson, David L. Robertson, Sepideh Sadegh, Joshua B. Singer, Kristof Theys, Chris Upton, Marius Welzel, Lowri Williams, Manja Marz

Subject: Biology And Life Sciences, Virology Keywords: virus bioinformatics; SARS-CoV-2; sequencing; epidemiology; drug design; tools

Online: 23 May 2020 (11:01:11 CEST)

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Preprint REVIEW | doi:10.20944/preprints202012.0242.v1

Long-Haul COVID-19: Putative Pathophysiology, Risk Factors, and Treatments

Shin Jie Yong

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; SARS-CoV-2; long-haul; inflammation; tissue damage; drug repurposing

Online: 10 December 2020 (09:42:20 CET)

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Preprint ARTICLE | doi:10.20944/preprints202309.0113.v1

Chronic Fatigue and Dis-Autonomy following COVID-19 Vaccination is Distinguished from Normal Vaccination Response by Altered Blood Markers

Amelie Semmler, Anna Katharina Mundorf, Anna Sabrina Kuechler, Karin Schulze-Bosse, Harald Heidecke, Kai Schulze-Forster, Matthias Schott, Markus Uhrberg, Sandra Weinhold, Karl J. Lackner, Marc Pawlitzki, Sven Guenther Meuth, Fritz Boege, Jana Ruhrländer

Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Post-Acute COVID-19 Vaccination Syndrome; PACVS, G-protein-coupled receptor; receptor antibody; interleukin-6; dis-autonomy; chronic fatigue.

Online: 4 September 2023 (07:14:41 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202004.0024.v1

Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment

Takahiko Koyama, Dilhan Weeraratne, Jane L. Snowdon, Laxmi Parida

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-nCoV-2; vaccine; antibody; immune escape; variant; spike protein; genomic drift; convalescent plasma

Online: 3 April 2020 (04:24:52 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0234.v1

Epidemiological Challenges in Pandemic Coronavirus Disease (COVID-19): Role of Artificial Intelligence

Abhijit Dasgupta, Abhisek Bakshi, Srijani Mukherjee, Kuntal Das, Soumyajeet Talukdar, Pratyayee Chatterjee, Sagnik Mondal, Puspita Das, Subhrojit Ghosh, Archisman Som, Pritha Roy, Rima Kundu, Akash Sarkar, Arnab Biswas, Karnelia Paul, Sujit Basak, Krishnendu Manna, Chinmay Saha, Satinath Mukhopadhyay, Nitai P. Bhattacharyya, Rajat K. De

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: SIRD; Twitter; GHSI; Pre-symptomatic; EHR; Contact tracing; On-line survey; qRT-PCR; X-ray; CT/HRCT; CNN; Autoencoder; Drug affinity; CPI; and Inflation.

Online: 14 May 2020 (11:25:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202007.0108.v1

COVID-19: Comprehensive Synopsis of Suggested Pathophysiological Mechanisms and Repurposed Drugs

Mathijs Binkhorst, Annette K. Offringa, Johannes G. van der Hoeven

Subject: Medicine And Pharmacology, Pharmacy Keywords: COVID-19; SARS-CoV-2; coronavirus; hypothesis; pathophysiology; drug repurposing

Online: 7 July 2020 (02:50:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0097.v1

PyRosetta Jupyter Notebooks Teach Biomolecular Structure Prediction and Design

Kathy Le, Jared Adolf-Bryfogle, Jason Klima, Sergey Lyskov, Jason Labonte, Steven Bertolani, Shourya Roy Burman, Andrew Leaver-Fay, Brian Weitzner, Jack Maguire, Ramya Rangan, Matt Adrianowycz, Rebecca Alford, Aleexan Adal, Morgan Nance, Rhiju Das, Roland Dunbrack, William Schief, Brian Kuhlman, Justin Siegel, Jeffrey Gray

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Protein structure and dynamics; Molecular structure and modeling; Protein and macromolecules; Computational methods and bioinformatics; Computer-based teaching tools; Learning materials and teaching tools; Multimedia teaching tools

Online: 7 February 2020 (11:42:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0165.v2

The Covid-19 Virus Double Pathogenic Mechanism. A New Perspective

Carlo Brogna

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Covid-19; Blastn; toxins protein; ACh; aChE; BuChE; CBP; Zero Point; bungaro-toxins, phospholipase A2; similar prothrombin activator protein

Online: 19 April 2020 (06:51:53 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0042.v2

Virtual Screening of Inhibitors Against Spike Glycoprotein of SARS-CoV-2: A Drug Repurposing Approach

Kanishka Senathilake, Sameera Samarakoon, Kamani Tennekoon

Subject: Biology And Life Sciences, Virology Keywords: Flue; Virus; COVID19; SARS CoV-2; Spike Protein; Virtual Screening; dgitoxin; anthracycline; rolitetracycline; E-155

Online: 23 March 2020 (10:19:17 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0071.v1

Drug and Vaccine Design against Novel Coronavirus (2019-nCoV) Spike Protein through Computational Approach

Suresh Kumar

Subject: Biology And 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)

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Preprint REVIEW | doi:10.20944/preprints201910.0144.v6

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

Petter I. Andersen, Aleksandr Ianevski, Hilde Lysvand, Astra Vitkauskiene, Valentyn Oksenych, Magnar Bjoras, Kaidi Telling, Irja Lutsar, Uga Dumpis, Yasuhiko Irie, Tanel Tenson, Anu Kantele, Denis E. Kainov

Subject: Biology And Life Sciences, Virology Keywords: virus; antiviral drug; drug discovery; drug development; broad-spectrum antivirals

Online: 14 February 2020 (02:27:24 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0447.v1

An Evolutionary RGD Motif in the Spike Protein of SARS-CoV-2 may Serve as a Potential High Risk Factor for Virus Infection?

Shijia Yan, Haixia Sun, Xianzhang Bu, Guohui Wan

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; ACE2; RGD; Spike protein; therapeutic drugs

Online: 28 February 2020 (16:26:53 CET)

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Working Paper HYPOTHESIS

Could Protein Malnutrition of Rapid Onset Explain the Atypical Symptoms of COVID-19 and Consequential Malfunctioning of the Body? A Hypothesis.

Maralyn Green

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: malnutrition; COVID-19; protein; immune system; SARS-CoV-2; cell proliferation; starvation

Online: 22 September 2020 (08:32:14 CEST)

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Preprint REVIEW | doi:10.20944/preprints202010.0179.v1

Explicit Treatment of Non Michaelis-Menten and Atypical Kinetics in Early Drug Discovery

Bharath Srinivasan

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Non Michaelis-Menten Kinetics; High-throughput screening; allostery; cooperativity; processive kinetics; distributive kinetics; single-molecule; auto-catalytic; drug discovery

Online: 8 October 2020 (13:34:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201609.0074.v1

Regulation of ERK and AKT Pathways by Hepatitis B Virus X Protein via Notch1 Pathway in Hepatocellular Carcinoma

Bo Liao, Hong-Hao Zhou, Hui-Fang Liang, Chang-Hai Li

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: hepatocellular carcinoma; hepatitis B virus X protein; Notch1 pathway; ERK; AKT

Online: 21 September 2016 (09:49:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0243.v1

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress

Anitra C. Carr, Emma Spencer, Liane Dixon, Steve Chambers

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: vitamin C; ascorbic acid; ascorbate; pneumonia; community acquired pneumonia; oxidative stress; protein carbonyls; hypovitaminosis C; vitamin C deficiency

Online: 15 April 2020 (10:12:26 CEST)

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Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

Preprint ARTICLE | doi:10.20944/preprints202006.0326.v1

Investigating Potential Inhibitory Effect of Uncaria tomentosa (Cat's claw) against the Main Protease 3CL^Pro of SARS-CoV-2 by Molecular Modeling

Andres F. Yepes-Pérez, Oscar Herrera-Calderon, José-Emilio Sánchez-Aparicio, Laura Tiessler-Sala, Jean-Didier Maréchal, Wilson Cardona-G

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: 2019-nCoV; 3CLpro protein; Cat's Claw; Uncaria tomentosa; Molecular Modeling

Online: 28 June 2020 (09:05:54 CEST)

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Preprint ARTICLE | doi:10.3390/sci2020045

Antimalarial Drugs in Ghana: A Case Study on Personal Preferences

Prince Yeboah, Arnold Donkor Forkuo, Obed Kwabena Offe Amponsah, Nana Ofori Adomako, Ahmad Yaman Abdin, Muhammad Jawad Nasim, Pitsch Werner, Anto Berko Panyin, Eike Emrich, Claus Jacob

Subject: Medicine And Pharmacology, Tropical Medicine Keywords: adverse drug reactions; antimalarial; Ghana; herbal remedies; malaria; questionnaire; street sale; orthodox; unnatural medicines; patient preference

Online: 12 June 2020 (00:00:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0407.v1

The SARS-CoV-2 Spike Protein D614G Mutation Shows Increasing Dominance and May Confer a Structural Advantage to the Furin Cleavage Domain

Leyan Tang, Allison Schulkins, Chun-Nan Chen, Kurt Deshayes, John S. Kenney

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; spike protein; D614G mutation; genotype distribution; furin cleavage site; secondary structure; sequence analysis; homology modeling

Online: 24 May 2020 (20:31:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0242.v1

A Putative Prophylactic Solution for COVID-19: Development of Novel Multiepitope Vaccine Candidate against SARS‐COV‐2 by Comprehensive Immunoinformatic and Molecular Modelling Approach

Hafiz Muzzammel Rehman, Muhammad Usman Mirza, Mahjabeen Saleem, Matheus Froeyen, Sarfraz Ahmad, Roquyya Gul, Muhammad Shahbaz Aslam, Muhammad Sajjad, Munir Ahmad Bhinder

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; spike protein; multiepitope vaccine; molecular modeling

Online: 15 March 2020 (12:45:54 CET)

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Working Paper ARTICLE

Macromolecular Modeling and Design in Rosetta: New Methods and Frameworks

Julia Koehler Leman, Brian D Weitzner, Steven M Lewis, RosettaCommons Consortium, Richard Bonneau

Subject: Chemistry And Materials Science, Theoretical Chemistry Keywords: structure prediction; Rosetta; computational modeling; protein design

Online: 16 October 2019 (05:40:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0397.v1

Genetic Uniformity of a Specific Region in SARS-CoV-2 Genome and In-Silico Target-Oriented Repurposing of N-Acetyl-D-Glucosamine

Omur Baysal, Ragip Soner Silme, Cagatay Karaaslan

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; Drug repurposing; N-acetyl-D-glucosamine; ORF1ab; Biodata mining; Protein modelling

Online: 24 May 2020 (18:49:41 CEST)

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Working Paper REVIEW

Immunogenicity of Clinically Relevant SARS-CoV-2 Vaccines in Non-human Primates and Humans

P.J. Klasse, D. F. Nixon, J. P. Moore

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; T-cells; vaccines; animal models; Operation Warp Speed

Online: 27 October 2020 (11:25:32 CET)

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Preprint ARTICLE | doi:10.20944/preprints201909.0273.v2

Disentangling the Amyloid Pathways: A Mechanistic Approach to Etiology

Maja Malmberg, Tarja Malm, Oskar Gustafsson, Anthony Wright, Samir El Andaloussi, Anders Linden, Kariem Ezzat

Subject: Biology And Life Sciences, Biophysics Keywords: amyloid; virus; nucleation; loss-of-function; Alzheimer's; Parkinson's; prion; protein-only

Online: 19 November 2019 (03:53:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints201705.0015.v1

Expression of Pokeweed Antiviral Protein Isoform S1 (PAP-S1) and of Ricin-A-Chain/PAP-S1 Novel Fusion Protein (RTA/PAP-S1) in Escherichia coli and Their Comparative Inhibition of Protein Synthesis in Vitro

Yasser Hassan, Sherry Ogg

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: fusion proteins; protein therapeutics; ricin; pokeweed antiviral protein; protein engineering; immunotoxins; ribosome-inactivating proteins.

Online: 1 May 2017 (10:51:21 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201610.0025.v1

A Protocol for Identifying Potentially Repurposable Drugs Using Online Tools and Databases

Aditi Chattopadhyay, Madhavi Ganapathiraju

Subject: Medicine And Pharmacology, Other Keywords: drug repurposing; translational bioinformatics; transcriptomics; transcriptome analysis; drug discovery; protocol; gene expression

Online: 9 October 2016 (08:42:23 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202010.0481.v1

Methylphenidate and Alprazolam Co-Abuse: Drug-DNA Interactions

Shweta Sharma, Meenu Dutt, Neha Sharma, Ravinder Naik Dharavath, Tanzeer Kaur

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Drug-DNA interaction; FTIR; Polydrug-abuse; UV-visible spectrophotometer

Online: 23 October 2020 (10:36:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201611.0075.v3

A Robust Liquid Chromatographic Method for Confirmation of Drug Stability of Azithromycin in Bulk Samples, Tablets and Suspensions

Alex O. Okaru, Kennedy O. Abuga, Franco N. Kamau, Stanley N. Ndwigah, Dirk W. Lachenmeier

Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: azithromycin; HPLC; robust; isocratic; drug stability; degradation products

Online: 4 January 2017 (10:08:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0234.v1

Sequence Properties of the MAAP Protein and of the VP1 Capsid Protein of Adeno-Associated Viruses

David G. Karlin

Subject: Biology And Life Sciences, Virology Keywords: adeno-associated virus; protein sequence analysis; overlapping genes; amino acid depletion; cysteine depletion; tyrosine depletion; capsid design; membrane-binding amphipathic helix

Online: 17 February 2020 (02:42:39 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0450.v1

Novel Mutations in the S1 domain of COVID 19 Spike Protein of Isolate from Gujarat Origin, Western India

Arup Kumar Banerjee, Feroza Begum, Dluya Thagriki, Prem Prakash Tripathi, Upasana Ray

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; S protein; RBD; S1; S2; Mutation

Online: 24 April 2020 (14:19:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201704.0005.v1

High-Performance Microcrystalline Cellulose/Soy Protein Isolate-Based Nanocomposite Film via Cu and Zn Nanoclusters Modification

Kuang Li, Shicun Jin, Hui Chen, Jing He, Jianzhang Li

Subject: Chemistry And Materials Science, Biomaterials Keywords: Soy protein isolate; Microcrystalline cellulose; Metal nanoclusters; Nanocomposite film; Tensile strength

Online: 3 April 2017 (16:42:12 CEST)

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Preprint REVIEW | doi:10.20944/preprints202008.0225.v1

Heat Stability of Proteins and Its Exploitation for Purification of Heat-Stable Proteins

Muhammad Ahmad, Aisha Tahir, Rana Salman Anjum

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Heat-stable proteins; Heat treatment; Hyperthermophilic proteins; Heat stability; Protein purification

Online: 9 August 2020 (22:00:46 CEST)

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Working Paper ARTICLE

Short-Term Moderate-Dose Corticosteroid Plus Immunoglobulin Effectively Reverses COVID-19 Patients Who Have Failed Low-Dose Therapy

Zhi-Guo Zhou, Shu-Min Xie, Jing Zhang, Fang Zheng, Di-Xuan Jiang, Ke-Yu Li, Qi Zuo, Yu-Sheng Yan, Ji-Yang Liu, Yuan-Lin Xie, Hong Peng, Lei Zhang

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: humans; infection control; therapy; coronavirus; immunoglobulins; drug therapy; therapeutic use; corticosteroid

Online: 8 March 2020 (17:04:19 CET)

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Background: The coronavirus disease-19 (COVID-19) has spread globally with more than 80,000 people infected, and nearly 3000 patients died. Currently, we are in an urgent need for effective treatment strategy to control the clinical deterioration of COVID-19 patients. Methods: The clinical data of 10 COVID-19 patients receiving short-term moderate-dose corticosteroid (160mg/d) plus immunoglobulin (20g/d) were studied in the North Yard of The First Hospital of Changsha, Hunan from January 17^th to February 27^th, 2020. Epidemiological, clinical, laboratory, radiological findings were analyzed. Results: After treatment with combination of low-dose corticosteroid (40-80mg/d) and immunoglobulin (10g/d), patients’ lymphocyte count (0.88±0.34 vs 0.59±0.18, P<0.05), oxygenation index including SPO₂ (94.90±2.51 vs 90.50±5.91, P<0.05) and PaO₂/FiO₂ (321.36±136.91 vs 129.30±64.97, P<0.05) were significantly lower than pre-treatment, and CT showed that the pulmonary lesion deteriorated in all patients. While after treatment of short-term moderate-dose corticosteroid plus immunoglobulin, patients’ APACHE Ⅱ score (9.10±6.15 vs 5.50±9.01, P<0.05), body temperature (37.59±1.16 vs 36.46±0.25, P<0.05), lymphocyte count (0.59±0.18 vs 1.36±0.51, P<0.05), Lactate dehydrogenase (419.24±251.31 vs 257.40±177.88, P<0.05), and C-reactive protein (49.94±26.21 vs 14.58±15.25, P<0.05) significantly improved compared with post-treatment with low-dose therapy. In addition, oxygenation index including SPO₂ (90.50±5.91 vs 97.50±1.18, P<0.05), PaO₂ (60.47±14.53 vs 99.07±34.31, P<0.05), and PaO₂/FiO₂ (129.30±64.97 vs 340.86±146.72, P<0.05) significant improved. Furthermore, CT showed that pulmonary lesions obviously improved in 7 patients. After systematic therapy, 4 out of 10 COVID-19 patients recovered and discharged. Conclusions: Short-term moderate-dose corticosteroid plus immunoglobulin is effective for reversing the continued deterioration of COVID-19 patients who failed to respond to the low-dose therapy. Funding: This work was supported by the Innovative Major Emergency Project Funding against the New Coronavirus Pneumonia in Hunan Province (Dr. Ji-Yang Liu, number 2020SK3014; Dr. Yuan-Lin Xie, number 2020SK3013).

Preprint REVIEW | doi:10.20944/preprints201712.0170.v1

Life Emerged from [GADV]-Protein World, but Not from RNA World!?

Kenji Ikehara

Subject: Biology And Life Sciences, Life Sciences Keywords: RNA world; [GADV]-protein world; GADV hypothesis; origin of life; protein 0th-order structure; origin of protein; origin of genetic code; origin of gene

Online: 25 December 2017 (08:08:37 CET)

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Preprint REVIEW | doi:10.20944/preprints201805.0011.v1

Changing Trends in Computational Drug Repositioning

Jaswanth K. Yella, Suryanarayana Yaddanapudi, Yunguan Wang, Anil G. Jegga

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: computational drug repositioning; drug repositioning; drug repurposing; machine learning; deep learning; crowdsourcing; open innovation; drug discovery

Online: 1 May 2018 (12:27:22 CEST)

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Preprint REVIEW | doi:10.20944/preprints202105.0346.v1

Role of Artificial Intelligence and Machine Learning in Bioinformatics: Drug Discovery and Drug Repurposing

Sameer Quazi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: drug discovery; drug repurposing; bioinformatics; machine learning; artificial intelligence; biomedical discoveries etc.

Online: 14 May 2021 (15:17:50 CEST)

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Preprint REVIEW | doi:10.20944/preprints202101.0503.v1

Central Nervous System Depressant Drugs: Updated Review

Abdullah Alkattan, Eman Alsalameen, Amr Ahmed

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: CNS; Drug receptors; GABA; Cannabinoid; Opioid; Serotonin; Dopamine

Online: 25 January 2021 (14:15:20 CET)

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Preprint REVIEW | doi:10.20944/preprints202306.1903.v1

Exploring Autophagy in Treating Spike Protein-related Pathology

Matthew T.J. Halma, Paul E. Marik, Yusuf M. Saleeby

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Fasting; autophagy; long-COVID; post-vaccination syndrome; spike protein; mitochondria; mitophagy

Online: 27 June 2023 (12:33:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201612.0068.v2

Classical and Novel TSPO Ligands for the Mitochondrial TSPO can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Nasra Yasin, Leo Veenman, Sukhdev Singh, Maya Azrad, Julia Bode, Alex Vainshtein, Bea Caballero, Ilan Marek, Moshe Gavish

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: modulation of nuclear gene expression; mitochondrial 18 kDa translocator protein (TSPO); TSPO ligand; PK 11195; 2-Cl-MGV-1; retrograde mitochondrial-nuclear signaling pathway; microscopy; mitochondria; cell nucleus

Online: 17 March 2017 (17:28:28 CET)

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Preprint ARTICLE | doi:10.20944/preprints202006.0165.v1

Evolutionary Origin of SARS-CoV-2 (COVID-19 Virus) and SARS Viruses through the Identification of Novel Protein/DNA Sequence Features Specific for Different Clades of Sarbecoviruses

Radhey S. Gupta, Bijendra Khadka

Subject: Biology And Life Sciences, Virology Keywords: conserved signature indels specific for SARS and SARS-CoV-2 viruses; DNA and Protein markers distinguishing different clades of Sarbecoviruses; evolutionary origin of SARS and SARS-CoV-2 viruses

Online: 14 June 2020 (04:09:39 CEST)

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Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2 and its relation to other viruses, protein sequences from sarbecoviruses were analyzed to identify conserved inserts or deletions (termed CSIs) demarcating either particular clusters/lineages of sarbecoviruses or those shared by specific lineages shedding light on their interrelationships. We report several clade-specific CSIs in the spike (S) and nucleocapsid (N) proteins that reliably demarcate distinct sarbecoviruses clades providing important insights into the origin and evolution of SARS-CoV-2. Two CSIs in the N-terminal domain (NTD) of S-protein are uniquely shared by SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs (SARS-CoV-2r cluster); another CSI supports a closer relationship of SARS-CoV-2 to BatCov-RaTG13. Three additional CSIs in the NTD are specific for two Bat-SARS-like CoVs (viz. CoVZXC21 and CoVZC45; CoVZC cluster) which form an outgroup of the SARS-CoV-2r cluster. Interestingly, one of the pangolin-CoV-MP789 also shares these CSIs but lack the CSIs specific for the SARS-CoV-2r cluster. The N-terminal sequence (aa 1-320) of the S-protein for pangolin-CoV-MP789 shows highest similarity (85.94%) to the CoVZC cluster, while its C-terminal region including the receptor binding domain (RBD) is most similar (97-98% identity) to the SARS-CoV-2 virus. These observations indicate that the spike protein sequence for the strain MP789 is of chimeric origin. Multiple CSIs described here also distinguish two bat SARS-CoVs strains (BM48-31/BGR/2008 and SARS_BtKY72) from all others. Our work also clarifies that two large CSIs (5 aa and 13 aa) found in the RBD of S-protein are mainly specific for the SARS and SARS-CoV-2r clusters of CoVs. The surface loops formed by these CSIs are predicted to be important in the binding of S-protein with the human ACE-2 receptor. Lastly, we have mapped the locations of different CSIs in the structure of the S-protein. These studies reveal that the three CSIs specific for the SARS-CoV-2r cluster form distinct surface-exposed loops/patches on the S-protein. As the surface-exposed loops play important roles in mediating novel interactions, the novel lobes/patches formed by the SARS-CoV-2-specific CSIs in the spike protein are predicted to play important roles in the interaction of this protein with other surface-exposed components in the host cells thereby enhancing the binding/infectivity of this virus to humans.

Preprint REVIEW | doi:10.20944/preprints202003.0345.v2

Widely Available Lysosome Targeting Agents Should Be Considered as a Potential Therapy for COVID-19

Jan Homolak, Ivan Kodvanj

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; lysosomotropic agents; endosome; antiviral; drug repurposing

Online: 24 March 2020 (06:26:54 CET)

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While the COVID-19 pandemic advances, the scientific community struggles in the search for treatments. Several improvements have been made, including the discovery of clinical efficacy of chloroquine (CQ) in COVID-19 patients, but the effective treatment protocols are still missing. In order to find novel treatment options many scientists utilize the in silico approach to identify compounds that could interfere with the key molecules involved in entrance, replication, or dissemination of the SARS-CoV-2. However, most of the identified molecules are currently not available as pharmacological agents, and assessing their safety and efficacy could take many months. Here, we took a different approach based on the proposed pharmacodynamic model of CQ in COVID-19. The main mechanism of action responsible for the favourable outcome of COVID-19 patients treated with CQ seems to be related to pH modulation-mediated effect on the endolysosomal trafficking, a characteristic of chemical compounds often called lysosomotropic agents because of the physico-chemical properties that enable them to passively diffuse through the endosomal membrane and undergo protonation-based trapping in the lumen of the acidic vesicles. In this review, we discuss lysosomotropic and lysosome targeting drugs that are already in clinical use and are characterized by good safety profiles, low cost, and wide availability. We emphasize that some of these drugs, in particular azithromycin and other macrolide antibiotics, indomethacin and some other non-steroidal anti-inflammatory drugs, proton pump inhibitors, and fluoxetine could provide additional therapeutic benefits in addition to the potential antiviral effect that still has to be confirmed by well-controlled clinical trials. As some of these drugs, mostly antibiotics, were already empirically used in the treatment of COVID-19, we encourage our colleagues all over the world to publish patient data so potential efficacy of these agents can be evaluated in the clinical context and rapidly implemented in the therapeutic protocols if the beneficial effect on clinical outcome is observed.

Preprint REVIEW | doi:10.20944/preprints201812.0170.v1

Nanocellulose in Biotechnology and Medicine: Focus on Skin Tissue Engineering and Wound Healing

Lucie Bacakova, Julia Pajorova, Marketa Bacakova, Anne Skogberg, Pasi Kallio, Katerina Kolarova, Vaclav Svorcik

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: bacterial nanocellulose; nanofibrillated nanocellulose; animal nanocellulose; algal nanocellulose; tissue engineering; tissue repair; wound dressing; cell delivery; drug delivery; antimicrobial properties

Online: 14 December 2018 (06:44:53 CET)

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Preprint REVIEW | doi:10.20944/preprints201611.0060.v1

The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide

Hong Kim, Eun-Hye Seo, Seung-Hyun Lee, Bum-Joon Kim

Subject: Chemistry And Materials Science, Biomaterials Keywords: cell-penetrating peptides (CPPs); reverse-transcriptase-subunit of telomerase (hTERT); GV1001; heat shock protein 90

Online: 11 November 2016 (09:59:30 CET)

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Preprint REVIEW | doi:10.20944/preprints202106.0377.v2

A Review of SARS-CoV-2, Responsible for COVID-19: History, Biology, Infection Mechanism, Antigenic Vaccines, Their Risks and how an Alternate RBD Vaccine is Safer?

Z.M.G. Sarwar Jahangir, Arleta Helena Marnik

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: aa = amino acids; ACE-2 = receptor angiotensin-converting enzyme 2; cDNA = complementary DNA; mRNA = messenger RNA; orf = open reading frame; RBD = receptor binding protein; S-protein = Spike protein; SARS-CoV-2 = severe respiratory syndrome coronavirus 2; Vaccines.

Online: 22 June 2021 (11:53:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0199.v1

Revealing SARS-CoV-2 Functional Druggability Through Multi-Target Cadd Screening of Repurposable Drugs

Yash Gupta, Dawid Maciorowski, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Ajay Bharti, Daniel Becker, Rathi Brijesh, Steven B Bradfute, Ravi Durvasula, Prakasha Kempaiah

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; CADD; virtual screening; approved drugs; drug repurposing; essential targets; molecular docking; molecular dynamics simulations

Online: 11 May 2020 (13:14:18 CEST)

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The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Preprint ARTICLE | doi:10.20944/preprints201610.0121.v1

TGF-β and Physiological Root Resorption of Deciduous Teeth

Emi Shimazaki, Takeo Karakida, Ryuji Yamamoto, Saeko Kobayashi, Makoto Fukae, Yasuo Yamakoshi, Yoshinobu Asada

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: cytokine; gene expression; osteoclast; root resorption; pediatric dentistry; protein expression

Online: 27 October 2016 (12:10:55 CEST)

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Preprint REVIEW | doi:10.20944/preprints202012.0062.v1

Recent Advances in Trop 2 Targeted Therapy for Solid Tumors

Shutan Liao, Bing Wang, Rong Zeng, Haifeng Bao, Xiaomin Chen, Rakesh Dixit, Xiaoyan Xing

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Trop 2; targeted therapy; antibody-drug conjugate; solid tumors

Online: 2 December 2020 (12:35:36 CET)

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Preprint ARTICLE | doi:10.20944/preprints201609.0001.v1

ESWT Enhances Expression of Pdia-3 which is a Key Factor of 1α,25-Dihydroxyvitamin D3 Rapid Membrane Signaling Pathway in Treatment of Early Osteoarthritis Knee

Shan-Ling Hsu, Jai-Hong Cheng, Ching-Jen Wang, Jih-Yang Ko, Chih-Hsiang Hsu

Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: protein-disulfide isomerase-associated 3; osteoarthritis; extracorporeal shockwave therapy; 1α,25-Dihydroxyvitamin D3 signaling pathway; two dimensional electrophoresis

Online: 1 September 2016 (10:47:39 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201701.0134.v1

CO₂-Induced Changes in Wheat Grain Composition: Meta-Analysis and Response Functions

Malin C. Broberg, Petra Högy, Håkan Pleijel

Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: Triticum aestivum; carbon dioxide; minerals; protein; starch; baking properties; crop quality; food security

Online: 31 January 2017 (11:49:41 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0372.v1

Structural Genomics and Interactomics of 2019 Wuhan Novel Coronavirus, SARS-CoV-2, Indicate Evolutionary Conserved Functional Regions of Viral Proteins

Hongzhu Cui, Ziyang Gao, Ming Liu, Senbao Lu, Winnie Mkandawire, Oleksandr Narykov, Suhas Srinivasan, Mo Sun, Dmitry Korkin

Subject: Biology And Life Sciences, Virology Keywords: structural genomics; protein-protein interactions; structural bioinformaticscomparative modeling; functional annotation; antiviral design; SARS-CoV-2; 2019-nCoV

Online: 25 February 2020 (11:24:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202009.0459.v1

SARS-CoV-2 Infections - Gene Expression Omnibus (GEO) Data Mining, Pathway Enrichment Analysis, and Prediction of Repurposable Drugs/Compounds

Srilakshmi Chaparala, Carrie L Iwema, Ansuman Chattopadhyay

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; coronavirus; drug repositioning; pathway enrichment

Online: 19 September 2020 (11:34:12 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0320.v1

Molecular Analyses of Over Hundred Sixty Clinical Isolates of SARS-CoV-2: Insights on Likely Origin, Evolution and Spread, and Possible Intervention

Salma Jamal, Jasdeep Singh, Javaid Ahmad Sheikh, Hina Singh, Mohd Khubaib, Sunil Kohli, Ulrich Dobrindt, Syed Asad Rahman, Nasreen Zafar Ehtesham, Seyed Ehtesham Hasnain

Subject: Biology And Life Sciences, Virology Keywords: envelope protein; furin cleavage site; hydrophobic aggregation and rapid transmission; immediate ancestor; pangolins coronaviruses; SARS-CoV-2; spike protein

Online: 23 March 2020 (00:42:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints201703.0232.v1

The Transmembrane Morphogenesis Protein gp1 of Filamentous Phages Contains Walker A and Walker B Motifs Essential for Phage Assembly

Belinda Loh, Maximilian Haase, Lukas Mueller, Andreas Kuhn, Sebastian Leptihn

Subject: Biology And Life Sciences, Virology Keywords: Filamentous phage; M13; gp1; Zonula occludens toxin (Zot); phage assembly; assembly 27 complex; ATPase; membrane protein; molecular hinge; secretion; Walker motifs

Online: 31 March 2017 (11:13:40 CEST)

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Preprint REVIEW | doi:10.20944/preprints201608.0043.v1

Arms Race between Enveloped Viruses and the Host ERAD Machinery

Dylan A. Frabutt, Yong-Hui Zheng

Subject: Biology And Life Sciences, Virology Keywords: enveloped viruses; viral glycoproteins; endoplasmic reticulum-associated degradation; ERAD; unfolded protein response; UPR; ER stress

Online: 4 August 2016 (11:44:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201805.0178.v1

Graph Coloring: A Novel Heuristic Based on Trailing Path; Properties, Perspective and Applications in Structured Networks

Abhirup Bandyopadhyay, Amit Kumar Dhar, Sankar Basu

Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: chromatic number; graph partitioning; NP to P; motif identifier; protein design

Online: 11 May 2018 (08:58:35 CEST)

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Graph coloring is a manifestation of graph partitioning, wherein, a graph is partitioned based on the adjacency of its elements. Partitioning serves potentially as a compartmentalization for any structural problem. Vertex coloring is the heart of the problem which is to find the chromatic number of a graph. The fact that there is no general efficient solution to this problem that may work unequivocally for all graphs opens up the realistic scope for combinatorial optimization algorithms to be invoked. The algorithmic complexity of graph coloring is non-deterministic in polynomial time (NP) and hard. To the best of our knowledge, there is no algorithm as yet that procures an exact solution of the chromatic number comprehensively for any and all graphs within the polynomial (P) time domain. However, several heuristics as well as some approximation algorithms have been attempted to obtain an approximate solution for the same. Here, we present a novel heuristic, namely, the 'trailing path', which returns an approximate solution of the chromatic number within polynomial time, and, with a better accuracy than most existing algorithms. The ‘trailing path’ algorithm is effectively a subtle combination of the search patterns of two existing heuristics (DSATUR and Largest First), and, operates along a trailing path of consecutively connected nodes (and thereby effectively maps to the problem of finding spanning tree(s) of the graph) during the entire course of coloring, where essentially lies both the novelty and the apt of the current approach. The study also suggests that the judicious implementation of randomness is one of the keys towards rendering an improved accuracy in such combinatorial optimization algorithms. Apart from the algorithmic attributes, essential properties of graph partitioning in random and different structured networks have also been surveyed, followed by a comparative study. The study reveals the remarkable stability and absorptive property of chromatic number across a wide array of graphs. Finally, a case study is presented to demonstrate the potential use of graph coloring in protein design – yet another hard problem in structural and evolutionary biology.

Preprint REVIEW | doi:10.20944/preprints201609.0091.v1

A Review of the 3D Designing of Scaffolds for Tissue Engineering with a Focus on Keratin Protein

Aarti Baliga, Shashikant Borkar

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: biomaterial; scaffold; protein; keratin; tissue engineering

Online: 26 September 2016 (10:25:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201611.0126.v3

IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

Deborah Rotoli, Natalia Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: IQGAP1; glioblastoma multiforme (GBM); scaffold protein; podosome/invadosome

Online: 16 January 2017 (10:30:48 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0466.v1

Angiotensin Converting Enzyme 2 in Coronavirus Disease (COVID-19): Evidence from Bioinformatics Analysis

Xiaomei Yang, Hongjin Zhao, Yan Li, Peng Zhang

Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: COVID-19; coronavirus; ACE2; bioinformatics analysis; drug prediction

Online: 26 April 2020 (03:14:50 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201703.0150.v1

Chemical Characterization of Olive Pomace in the Northern Region of Jordan

Mohammed Wedyan, Bilal Abu Hanieh, Ahmed Al Harahsheh

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: olive pomace oil; fatty acid profile; total nitrogen content; total protein; olive pomace; biochemical characterization

Online: 20 March 2017 (08:40:46 CET)

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Preprint ARTICLE | doi:10.20944/preprints201809.0544.v1

Peak Week and Competition Day Strategies of Competitive Natural Bodybuilders

Andrew J Chappell , Trevor Simper

Subject: Biology And Life Sciences, Food Science And Technology Keywords: Bodybuilding; Drug Free; Competing; Peaking; Carbohydrate Loading; Water Loading; Sodium Loading; Fat Loading: Vitamin C; Fibre Restriction

Online: 27 September 2018 (12:58:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202107.0531.v1

HALO-RPD: In Searching for RNA-Binding Protein Targets in Plants

Anastasia Shamustakimova

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: A.thaliana; HaloTag; RNA-binding proteins; RNA pulldown assay; RNA-protein complexes; cold shock domain protein

Online: 23 July 2021 (09:32:28 CEST)

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Preprint REVIEW | doi:10.20944/preprints201908.0120.v1

QTLs identified for Biofortification Traits in Wheat: A Review

Pooja Devi, Prashant Kaushik, Dinesh Kumar Saini

Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: wheat; biofortification; QTLs; protein; minerals

Online: 9 August 2019 (12:54:32 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201704.0023.v1

Effects of Biomimetic Shear Stress by Self-Assembled Gelatin Oleic Nanoparticles Containing Paclitaxel on the Behavior of Cancer Cell Lines in a Microfluidic System

Taehee Kang, Thuy Thi Thanh Tran, Kyung Taek Oh, Han-Gon Choi, Beom-Jin Lee

Subject: Chemistry And Materials Science, Nanotechnology Keywords: gelatin-oleic conjugate; self-assembled biodegradable nanoparticles; biomimetic shear stress; cell dynamic environment; cellular drug delivery; paclitaxel

Online: 4 April 2017 (10:59:02 CEST)

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Preprint REVIEW | doi:10.20944/preprints201702.0036.v1

Nanoparticle-Mediated Drug Delivery System for Pulmonary Arterial Hypertension

Kazufumi Nakamura, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Norifumi Kawakita, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Nobuhiro NIshii, Hiroshi Ito

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: pulmonary arterial hypertension; prostacyclin; nanoparticle; drug delivery system

Online: 13 February 2017 (09:27:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0535.v1

Novel Polybasic Cleavage Site in SARS-CoV-2 Genome Is Likely to Induce a Major Change in the RNA Secondary Structure

Amirhossein Manzourolajdad, Zhenming Xu, Diako Ebrahimi

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2 RNA Secondary Structure; Spike Protein; Furin; TMPRSS2

Online: 30 April 2020 (14:13:36 CEST)

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Working Paper REVIEW

Phage Assisted Continuous Evolution (PACE): A How-to Guide for Directed Evolution

Serban C. Popa, Ichiro Inamoto, Benjamin W. Thuronyi, Jumi A. Shin

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: continuous evolution; protein design; protein engineering; phage; bacterial one-hybrid; plaque assay; mutational analysis; DNA sequencing

Online: 5 November 2019 (02:19:01 CET)

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Preprint REVIEW | doi:10.20944/preprints202012.0708.v1

Phytochemicals as Therapeutics Against COVID-19: An In-Silico Study

Debraj Koiri, Ditam Chakraborty, Pranotosh Das, Rajkumar Rana, Soumyanil Chatterjee, Tanmoy Das, Paltu Kumar Dhal

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Phytochemicals; SARS-CoV-2; S-Protein; Molecular docking; ACE 2

Online: 28 December 2020 (16:51:12 CET)

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Preprint REVIEW | doi:10.20944/preprints202102.0466.v1

A Review on Response Mechanism of Plants to Drought Stress

Xinyi Yang, Meiqi Lu, Yvfei Wang, Yiran Wang, Zhijie Liu, Su Chen

Subject: Biology And Life Sciences, Plant Sciences Keywords: Drought stress; Osmotic regulation; LEA protein; ROS; Signaling; Drought-responsive gene

Online: 22 February 2021 (12:38:05 CET)

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Preprint ARTICLE | doi:10.20944/preprints201610.0083.v1

UPEI-400, a Conjugate of Lipoic Acid and Scopoletin, Mediates Neuroprotection in a Rat Model of Ischemia/Reperfusion

Barry J. Connell, Monique C. Saleh, Desikan Rajagopal, Tarek M. Saleh

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: stroke; antioxidant; co-drug; animal model

Online: 20 October 2016 (08:46:38 CEST)

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Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Preprint ARTICLE | doi:10.20944/preprints201809.0383.v1

Achieving a Good Crystal System for Crystallographic X-ray Fragment Screening

Patrick M. Collins, Alice Douangamath, Romain Talon, Alexandre Dias, José Brandão-Neto, Tobias Krojer, Frank von Delft

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: fragment screening; XChem; protein crystallisation; X-ray crystallography; diamond light source; I04-1; structural genomics consortium

Online: 19 September 2018 (11:37:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201705.0173.v1

Molecular and Biochemical Characterization of Calmodulin from Echinococcus granulosus

Ning Wang, Xiu-Qin Zhong, Xing-Ju Song, Xiao-Bin Gu, Wei-Ming Lai, Yue Xie, Xue-Rong Peng, Guang-You Yang

Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Echinococcus granulosus; Calmodulin; Ca2+-binding protein; Immunohistochemical localization; Quantitative RT-PCR

Online: 24 May 2017 (08:07:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201702.0052.v1

Simplified Swarm Optimization Based Function Modules Detection in Protein-to-Protein Interaction Networks

Xianghan Zheng, Lingting Wu, Shaozhen Ye, Riqing Chen

Subject: Computer Science And Mathematics, Information Systems Keywords: protein–protein interaction networks; protein function module; simplified swarm optimization

Online: 15 February 2017 (10:17:35 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202106.0238.v1

Role of N501Y Mutation in SARS-CoV-2 Spike Protein Structure

Urmi Roy

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Immunoinformatics; Molecular dynamics simulation; mutation; SARS-CoV-2; Spike protein; Virus structure

Online: 8 June 2021 (13:57:03 CEST)

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Preprint REVIEW | doi:10.20944/preprints201801.0148.v1

Linoleic Acid Derivative DCP-LA Prevents Tau Phosphorylation by Targeting GSK-3β

Tomoyuki Nishizaki

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: DCP-LA; PKCε; protein tyrosine phosphatase 1B; Akt; GSK-3β; tauopathy

Online: 17 January 2018 (05:26:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints202006.0358.v1

In-Silico Analysis of Natural Products That Modulates Enzymes of Diabetic Target

Babita Aryal, Saroj Basnet, Bishnu P. Marasini, Karan Khadayat, Darbin Kumar Poudel, Ganesh Lamichhane, Prakriti Budhathoki, Purushottam Niraula, Sonika Dawadi, Rishab Marahatha, Sitaram Phuyal, Niranjan Parajuli

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Enzyme inhibition; Secondary Metabolites; In-silico Analysis; Molecular docking; Drug candidates

Online: 30 June 2020 (08:11:28 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0510.v1

A Structural View at SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping

Maria Romano, Alessia Ruggiero, Flavia Squeglia, Giovanni Maga, Rita Berisio

Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV-2; COVID19; RNA replication; protein structure; infectious disease

Online: 29 April 2020 (12:52:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201701.0105.v1

In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

Olivier Sandre, Coralie Genevois, Eneko Garaio, Laurent Adumeau, Stéphane Mornet, Franck Couillaud

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: magnetic hyperthermia; gene therapies; heat shock protein promoter; in vivo optical imaging; magnetic polymer-coated nanoparticles

Online: 24 January 2017 (04:14:19 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0393.v1

Virtual Screening and Molecular Dynamics Simulation Suggest Valproic Acid Co-A could Bind to SARS-CoV2 RNA Depended RNA Polymerase

Neel Sarovar Bhavesh, Anupam Patra

Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV2; RNA depended RNA polymerase; Valproic acid Co-A; drug repurposing

Online: 26 March 2020 (15:04:22 CET)

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Preprint ARTICLE | doi:10.20944/preprints201701.0059.v1

Optimization of Lactoperoxidase and Lactoferrin Separation on an Ion-Exchange Chromatography Step

Naeimeh Faraji, Yan Zhang, Ajay K. Ray

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cation exchange chromatography; minor milk protein; response surface modeling; simulation; steric mass action (SMA); optimization

Online: 12 January 2017 (09:59:40 CET)

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Preprint ARTICLE | doi:10.3390/sci1020055

Copper-to-Zinc Ratio Correlates with an Inflammatory Marker in Patients with Sickle Cell Disease

Mathias Emokpae, Emmanuel Fatimehin

Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: copper; c-reactive protein; inflammation; sickle cell disease; zinc

Online: 18 September 2019 (00:00:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201704.0028.v1

Synthesis of Europium-doped Fluorapatite Nanorods and Their Multifunctional Biomedical Applications

Hai Feng Zeng, Mu Yang Sun, Su Fan Wu, Hai Feng Chen

Subject: Chemistry And Materials Science, Nanotechnology Keywords: lanthanides; fluorapatite; drug loading; nano carrier

Online: 5 April 2017 (11:26:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201708.0015.v1

Omega-3 polyunsaturated fatty acids protect against ischemia-reperfusion renal injury through AMPK-mediated autophagy

Do Hyeong Gwon, Tae Woong Hwang, Ju-ye Ro, Yoon-Joong Kang, Jin Young Jeong, Do-Kyung Kim, Kyu Lim, Dong Woon Kim, Dae Eun Choi, Jwa-Jin Kim

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: ischemia-reperfusion injury (IRI), ω3-PUFA, AMP-activated protein kinase (AMPK), autophagy

Online: 4 August 2017 (12:56:08 CEST)

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