DOCSLIB.ORG

Molecular Docking Study of Some Nucleoside Analogs Against Main Protease of SARS-Cov-2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Molecular Docking Study of Some Nucleoside Analogs Against Main Protease of SARS-Cov-2 DOI: 10.14744/ejmo.2020.94995 EJMO 2020;4(4):324–335 Research Article Molecular Docking Study of Some Nucleoside Analogs against Main Protease of SARS-CoV-2 Abhijit Chhetri,1 Dhiraj Brahman2 1Department of Microbiology, St. Joseph’s College, Darjeeling, India 2Department of Chemisty, St. Joseph’s College, Darjeeling, India Abstract Objectives: The global pandemic outburst of SARS-CoV-2 in December 2019 infected a large number of people and hasclaimed a significant number of lives. Given the lack of proper therapeutic agents or vaccinefor this pandemic dis- ease, the world is faced with a huge challenge of curingthe infected patients. Therefore, the development of potential therapeutic agents against COVID-19 is a dire need of the situation. Methods: Herein, we utilized molecular docking to explore the inhibitory potential of nine nucleoside analogs, in- cludingTelbivudine, Entecavir, Clevudine, Zalcitabine, Taribavirin, Stavudine, Lamivudine, Cordycepin, and cordycepin triphosphate, against the main protease of SARS-CoV-2. Results: The binding energy (ΔG) ofthenine nucleoside analogs against the main protease of SARS-CoV-2 were −6.5 Kcal/mole (Telbivudine), −6.8 Kcal/mole (Entecavir), −6.8 Kcal/mole (Clevudine), −5.8 Kcal/mole (Zalcitabine),−6.1 Kcal/ mole (Taribavirin), −6.5 Kcal/mole (Stavudine), −5.7 Kcal/mole (lamivudine),−6.5 Kcal/mole(Cordycepin), and −6.9 Kcal/ mole (Cordycepin triphosphaye). Conclusion: Although the molecular docking results are promising, further in vitro and in vivo studies are required to understand the mechanism of binding of thesenucleoside analogs to the COVID-19 Protein. Keywords: Binding energy, COVID-19, Molecular Docking, nucleoside analog, SARS-CoV-2 protease Cite This Article: Chhetri A, Brahman D. Molecular Docking Study of Some Nucleoside Analogs against Main Protease of SARS-CoV-2. EJMO 2020;4(4):324–335. ARS-CoV-2 (Severe Acute Respiratory Syndrome Co- binding of the viral envelope-anchored spike protein with Srona Virus 2) or corona virus disease 2019 (COVID-19) the host receptor ACE2 (angiontensin-converting enzyme was reported from Wuhan city of China in December 2019 2), thereby causing the infection in the host.[4] There is still and the viral infection has been spreading rapidly around no vaccine or definite therapeutic agents for the treatment the world thereby making serious problems to the public of the infection caused by SARS-CoV-2.[5] Several antiviral health.[1] The World Health Organization (WHO), on March and antimalarial drugs, such as Favipiravir (Influenza), Rib- 11, 2020, recognized the disease as a global pandemic avirin (RSV infection and hepatitis C infection), Nelfinavir due to risingconcern about its fast spreading andcapac- (HIV infection), Lopinavir/ritonavir (HIV infection), remde- ity to transmit fromhuman to human.[2] Like SARS-CoV, sivir (Hepatitis Cand Sars-CoV-2 infection), Umifenoviror SARS-CoV-2 or COVID-19 belongs to the β genus of sin- Arbidol (Influenza), Chloroquine, and Hydroxychloroquine gle strand enveloped RNA virus (family of Coronaviridae), (malaria), have been used for the preliminary treatment which is responsible for acute lung injury accompanied of COVID-19.[6-11] Recently, a combination of three drugs, by acute respiratory distress syndrome.[3] Early scientific Lopinavir, Oseltamivir, and Ritonavirhas been formulated as investigations have shown that the entry of SARS-CoV as a therapeutic measure to manage the virulence to a great well as SARS-CoV-2 into the host cell occurs through the extent in COVID-19patients (The Scientist, February 3 2020, Address for correspondence: Dhiraj Brahman, MD. Department of Chemisty, St. Joseph’s College, Darjeeling, India Phone: +91-8101171795 E-mail: [email protected] Submitted Date: October 11, 2020 Accepted Date: November 10, 2020 Available Online Date: December 25, 2020 ©Copyright 2020 by Eurasian Journal of Medicine and Oncology - Available online at www.ejmo.org OPEN ACCESS This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. EJMO 325 https://www.the-scientist.com/news-opinion/flu-andan- Methods ti-hiv-drugs-show-efficacy-against-coronavirus-67052). However, these antiviral or antimalarial drugs have some Preparation of Protein limitations for the treatment of COVID-19. More over, so far, Crystal structures ofthemain protease (Mpr°) of SARS-CoV-2 there is no specific drug against COVID-19approved by the or COVID-19 with PDB ID: 6LU7wasretrieved through Pro- US Food and Drug Administration Agency.[12,13] There fore,- tein Data Bank (http://www.rcsb.org/).In order to prepare given the global pandemic situation, the world is in need of the receptor protein input files, Graphical User Interface highly efficient, minimal side effect, inexpensive, and read- program “Auto Dock Tools (ADT) 1.5.6” from Molecular ily available drugs against COVID-19. After the outburst of Graphics Laboratory developed by Scripps Research Insti- COVID-19, different research groups have been continu- tute wasused.[55] In a typical receptor protein preparation ously working in designing and formulating antiviral drugs for docking study, input file was generatedby taking the and vaccine to ascertain the therapeutic strategies for specific chain of the protein (Chain A) and removing wa- COVID-19.[14-22] Many of these research groups have report- ter molecules, ions, ligands, and subunits from the original ed the binding affinity of different natural products, fungal structure file. The receptor protein input.pdbqt filewaspre- secondary metabolites, FDA approved antiviral or antima- pared by addingpolar hydrogen atoms and Kollman united larial drugs, and food supplements, among others, toward atom charges into the receptor PDB file.[56] the main protease (6LU7) of COVID-19 through Molecular Preparation of Ligand Docking approach.[22-36] On the other hand, nucleoside an- alogs are, in recent times, found as a backbone of many The three dimensional structure of the nucleoside ana- drugs for the treatment of infection diseases caused by HIV, logs, includingTelbivudine (PubChem CID: 159269), Ente- hepatitis B or C viruses, and herpes viruses.[37,38] Interesting- cavir (PubChem CID: 135398508), Clevudine (PubChem ly, biological activity as well as the chemical and physical CID: 73115), Zalcitabine (PubChem CID: 24066), Taribavirin properties of nucleoside analog can be tuned remarkably (PubChem CID: 451448), Stavudine (PubChem CID: 18283), by simple alteration of the sugar moiety of nucleoside with Lamivudine (PubChem CID: 60825), cordycepin (PubChem different substituent and heteroatom, among others.[39] CID: 6303), and cordycepin triphosphate (PubChem CID: 65562), were downloaded in.sdf format from PubChem Moreover, the nucleoside analogs usually show antiviral ac- (http://pubchem.ncbi.nlm.nih.gov/) database and depict- tivities by inhibiting the viral replication through theblock- ed in Figure 1. The 3D structures in.sdf format of nucleo- age of cellular division or impairment of DNA/RNA synthe- side analogs were converted to standard.pdb file format sis or inhibition of cellular or viral enzymes activity.[40,41] The using online SMILES translator (https://cactus.nci.nih.gov/ nucleoside analogs Telbivudine (hepatitis B inhibiotor), translate/) and the input.pdbqt file was generated using Entecavir (HIV/ AIDS and Hepatitis B inhibitor), Clevudine ADT. Since the nucleoside analog drugswere non-peptides, (Hepatitis B inhibitor), Zalcitabine (reverse-transcriptase in- Gasteiger charge was assigned and non-polar hydrogens hibitor), Taribavirin (prodrug of Ribavirin), Stavudine (HIV/ were merged. AIDS inhibitors), Lamivudine (first-generation nucleoside reverse transcriptase inhibitor), Cordycepin (RNA synthesis Docking Study inhibitor), and Cordycepin Triphosphate (polyadenylation All docking simulations were performedin AutoDock Vina inhibitors, antineoplastic, antioxidant, and anti-inflamma- programme 1.1.2 developed by Scripps Research institute tory agent) have been used in thetreatment ofmany viral andresults of the docking study and intermolecular interac- diseases.[42-52] In recent times, bioinformatics have provid- tions between the receptors and nucleoside analogs were ed an alternative and innovative technique to combat this analyzed using BIOVIA Discovery Studio 2020 (DS) version problemof the design and manufacture of new drug mol- 20.1.0.0 (Dassault Systèmes BIOVIA, Discovery Studio Mod- ecule for specific diseases.[53] Molecular docking study pro- eling Environment, Release 2017, San Diego: Dassault Sys- vides an insight into the different types of intermolecular tèmes, 2016) and Edupymol version 1.7.4.4.[57,58] In a typical interactions between a target protein and its ligand in a docking simulation, three dimensional affinity (grid) maps three dimensional space; therefore, this method serves as and electrostatic grid boxes of dimension 50×50×50 Å a simple and alternative way in the process of designing, grid points and grid center (X, Y, Z) of −26.283, 12.599, and evaluating, and comparing new drugs.[54] Thus, in this arti- 58.966 with a spacing of 1.00 Åwere generated to cover the cle,an attempt has been made tostudy the binding affini- entire active site of the receptor protein. Lamarckian genet- ties as well as protein-ligand interaction of nine nucleoside ic algorithm and a standard protocol with default setting analogsagainst the main protease (6LU7) ofSARS-CoV-2. of other run parameters were used for the docking simula- 326 Chhetria et al., Molecular Docking
Load more

Recommended publications
  • Current Therapies for Chronic Hepatitis C
    Southern Illinois University Edwardsville SPARK Pharmacy Faculty Research, Scholarship, and Creative Activity School of Pharmacy 1-2011 Current Therapies for Chronic Hepatitis C McKenzie C. Ferguson Southern Illinois University Edwardsville, [email protected] Follow this and additional works at: https://spark.siue.edu/pharmacy_fac Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Ferguson, McKenzie C., "Current Therapies for Chronic Hepatitis C" (2011). Pharmacy Faculty Research, Scholarship, and Creative Activity. 4. https://spark.siue.edu/pharmacy_fac/4 This Article is brought to you for free and open access by the School of Pharmacy at SPARK. It has been accepted for inclusion in Pharmacy Faculty Research, Scholarship, and Creative Activity by an authorized administrator of SPARK. For more information, please contact [email protected],[email protected]. Chronic Hepatitis C & Current Therapies 1 Review of Chronic Hepatitis C & Current Therapies Reviews of Therapeutics Pharmacotherapy McKenzie C. Ferguson, Pharm.D., BCPS From the School of Pharmacy, Southern Illinois University Edwardsville, Department of Pharmacy Practice, Edwardsville, Illinois. Address for reprint requests : Southern Illinois University Edwardsville School of Pharmacy 220 University Park Drive, Ste 1037 Edwardsville, IL 62026-2000 Email: [email protected] Keywords : hepatitis C, HCV, ribavirin, interferon, peginterferon alfa-2a, peginterferon alfa-2b, albinterferon, taribavirin, telaprevir, therapeutic efficacy, safety The author received no sources of support in the form of grants, equipment, or drugs. Chronic Hepatitis C & Current Therapies 2 ABSTRACT Hepatitis C virus affects more than 180 million people worldwide and as many as 4 million people in the United States. Given that most patients are asymptomatic until late in disease progression, diagnostic screening and evaluation of patients that display high-risk behaviors associated with acquisition of hepatitis C should be performed.
    [Show full text]
  • Taribavirin.Pdf
    Virologic Response Rates of Weight-Based Taribavirin Versus Ribavirin in Treatment-Naive Patients with Genotype 1 Chronic Hepatitis C Fred Poordad,1 Eric Lawitz,2 Mitchell L. Shiffman,3 Tarek Hassanein,4 Andrew J. Muir,5 Bruce R. Bacon,6 Jamie Heise,7 Deanine Halliman,7 Eric Chun,7 and Janet Hammond7 Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C. The study aimed to determine if weight-based dosing of taribavirin (TBV), an oral prodrug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previ- ously demonstrated anemia advantage with fixed dose administration. A U.S. phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naive patients infected with genotype 1 who were stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/ day) or RBV (800-1400 mg/day) with pegylated interferon alfa-2b for 48 weeks. The SVR rates in this difficult-to-cure patient demographics (mean age, 49 years; 61% male; 30% African American or Latino; high viral load; advanced fibrosis; and mean weight, 82 kg) were 28.4%, 24.3%, 20.6%, and 21.4% in the 20, 25, and 30 mg/kg TBV groups and the RBV group, respectively. There were no statistical differences in the efficacy analyses. Ane- mia rates were significantly lower (P < 0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7%, respectively) compared to RBV (32.9%).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,871,799 B2 Adonato Et Al
    USOO8871799B2 (12) United States Patent (10) Patent No.: US 8,871,799 B2 adonato et al. (45) Date of Patent: Oct. 28, 2014 (54) IMINOCHROMENE ANTI-VIRAL the action of nucleophilic reagents. 5. Interactions of COMPOUNDS 2-Iminocoumarin-3-carboxamide with anthranilic acid and its derivatives. (2000) Chemistry of Heterocyclic COmpounds, vol. 36. (75) Inventors: Shawn P. Ladonato, Seattle, WA (US); pp. 1026-1031.* Kristin Bedard, Seattle, WA (US) Banerjee, S., et al. (2008) Multi-targeted therapy of cancer by genistein, Cancer Lett 269, 226-242. (73) Assignee: Kineta, Inc., Seattle, WA (US) Barnard, D. L. (2009) Animal models for the study of influenza pathogenesis and therapy, Antiviral Res 82, Al 10-122. (*) Notice: Subject to any disclaimer, the term of this Blight, J.J. et al., (2002) Highly Permissive Cell Lines for patent is extended or adjusted under 35 Subgenomic and Genomic Hepatitis C Virus RNA Replication, J. U.S.C. 154(b) by 55 days. Virology 76:13001-13014. Dafis, S., et al. (2008) Toll-like receptor 3 has a protective role (21) Appl. No.: 13/642,823 against West Nile virus infection, JVirol 82, 10349-10358. Horsmans, Y, et al. (2005) Isatoribine, an agonist of TLR7, reduces (22) PCT Filed: Apr. 20, 2011 plasma virus concentration in chronic hepatitis C infection, Hepatol ogy 42, 724-731. (86). PCT No.: PCT/US2011/033309 Johnson, C. L., and Gale, M., Jr. (2006) CARD games between virus S371 (c)(1), and host get a new player, Trends Immunol 27, 1-4. (2), (4) Date: Oct. 22, 2012 Kato, H., et al.
    [Show full text]
  • EASL - Beyond Protease Inhibitors Hep C Pipeline Filling Up
    April 04, 2011 EASL - Beyond protease inhibitors hep C pipeline filling up Amy Brown With the development of hepatitis C protease inhibitors boceprevir and telaprevir all but concluded, specialists in treating the liver disease now are looking beyond the two first-in-class drugs (see tables below). Research is focusing on a combination of molecules or even a single agent that can reduce the burden of treatment, combat a wider spectrum of virus genotypes, dodge viral resistance and succeed in more patients, particularly those who have not seen relief with existing therapies. A top priority among experts gathered at the EASL International Liver Congress is developing an interferon-free regimen, to eliminate the flu-like symptoms and other side effects common with the immunostimulant, a goal that seems tantalysingly just out of reach for patients and physicians. “The real success will probably be in five or six years when we’re able to combine different oral agents, different small molecules with different modes of action and maybe get rid of interferon,” says Antonio Craxi, professor of gastroenterology and internal medicine at the University of Palermo. Viral breakthrough For now, viral breakthrough has haunted therapies that have attempted trial arms without peginterferon-alfa and ribavirin, the antiviral that makes up the other half of the current standard of care. For example, viral breakthrough forced Vertex Pharmaceuticals to cancel an arm of its phase II trial of telaprevir and VX-222 that did not include a background standard of care therapy. The trial continues in the quadruple-therapy arm, with positive interim results presented at the conference.
    [Show full text]
  • Hepatitis C Virus Management: Potential Impact of Nanotechnology Mostafa H
    Elberry et al. Virology Journal (2017) 14:88 DOI 10.1186/s12985-017-0753-1 REVIEW Open Access Hepatitis C virus management: potential impact of nanotechnology Mostafa H. Elberry1,2, Noureldien H. E. Darwish1,3 and Shaker A. Mousa1* Abstract Around 170–200 million individuals have hepatitis C virus (HCV), which represents ~ 3% of the world population, including ~ 3–5 million people in the USA. According to the WHO regional office in the Middle East, Egypt has the highest prevalence in the world, with 7% prevalence in adults. There had been no effective vaccine for HCV; a combination of PEG-Interferon and ribavirin for at least 48 weeks was the standard therapy, but it failed in more than 40% of the patients and has a high cost and serious side effects. The recent introduction of direct-acting antivirals (DAA) resulted in major advances toward the cure of HCV. However, relapse and reduced antiviral efficacy in fibrotic, cirrhotic HCV patients in addition to some undesired effects restrain the full potential of these combinations. There is a need for new approaches for the combinations of different DAA and their targeted delivery using novel nanotechnology approaches. In this review, the role of nanoparticles as a carrier for HCV vaccines, anti-HCV combinations, and their targeted delivery are discussed. Keywords: Hepatitis C virus, Drug delivery system, HCV genotypes, Nanoparticles Background Until 2011, the standard treatment was a blend of From the time of its discovery in 1989, hepatitis C virus subcutaneous pegylated interferon (PEG-IFN) in (HCV) has been known globally as the primary reason addition to oral ribavirin (RBV), administered for 24 or for chronic liver disease [1].
    [Show full text]
  • Longitudinal Analysis of the Utility of Liver Biochemistry in Hospitalised COVID-19 Patients As Prognostic Markers
    medRxiv preprint doi: https://doi.org/10.1101/2020.09.15.20194985; this version posted September 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Longitudinal analysis of the utility of liver biochemistry in hospitalised COVID-19 patients as prognostic markers. Authors: Tingyan Wang1,2*, David A Smith1,3*, Cori Campbell1,2*, Steve Harris1,4, Hizni Salih1, Kinga A Várnai1,3, Kerrie Woods1,3, Theresa Noble1,3, Oliver Freeman1, Zuzana Moysova1,3, Thomas Marjot5, Gwilym J Webb6, Jim Davies1,4, Eleanor Barnes2,3*, Philippa C Matthews3,7*. Affiliations: 1. NIHR Oxford Biomedical Research Centre, Big Data Institute, University of Oxford 2. Nuffield Department of Medicine, University of Oxford 3. Oxford University Hospitals NHS Foundation Trust 4. Department of Computer Science, University of Oxford 5. Oxford Liver Unit, Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford University Hospitals 6. Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge 7. Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust *Equal Contributions Corresponding Author: Professor Eleanor Barnes, The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. Telephone: 01865 281547. Email: [email protected] Author Contributions: T.W, D.A.S, C.C., P.C.M and E.B contributed equally to this work. T.W, D.A.S and C.C performed the data analysis and wrote the manuscript and were supervised by E.B, P.C.M and J.D.
    [Show full text]
  • A Computational Approach to Aid Clinicians in Selecting Anti-Viral
    www.nature.com/scientificreports OPEN A computational approach to aid clinicians in selecting anti‑viral drugs for COVID‑19 trials Aanchal Mongia1, Sanjay Kr. Saha2, Emilie Chouzenoux3* & Angshul Majumdar1* The year 2020 witnessed a heavy death toll due to COVID‑19, calling for a global emergency. The continuous ongoing research and clinical trials paved the way for vaccines. But, the vaccine efcacy in the long run is still questionable due to the mutating coronavirus, which makes drug re‑positioning a reasonable alternative. COVID‑19 has hence fast‑paced drug re‑positioning for the treatment of COVID‑19 and its symptoms. This work builds computational models using matrix completion techniques to predict drug‑virus association for drug re‑positioning. The aim is to assist clinicians with a tool for selecting prospective antiviral treatments. Since the virus is known to mutate fast, the tool is likely to help clinicians in selecting the right set of antivirals for the mutated isolate. The main contribution of this work is a manually curated database publicly shared, comprising of existing associations between viruses and their corresponding antivirals. The database gathers similarity information using the chemical structure of drugs and the genomic structure of viruses. Along with this database, we make available a set of state‑of‑the‑art computational drug re‑positioning tools based on matrix completion. The tools are frst analysed on a standard set of experimental protocols for drug target interactions. The best performing ones are applied for the task of re‑positioning antivirals for COVID‑19. These tools select six drugs out of which four are currently under various stages of trial, namely Remdesivir (as a cure), Ribavarin (in combination with others for cure), Umifenovir (as a prophylactic and cure) and Sofosbuvir (as a cure).
    [Show full text]
  • Valeant Pharmaceuticals Grants Schering-Plough Exclusive Option in Japan for Taribavirin in Exchange
    [ Industry Watch ] JAPAN Valeant Pharmaceuticals Grants Schering-Plough Exclusive Option in Japan for Taribavirin in Exchange aleant Pharmaceuticals International announced that it has entered into an exclusive option agreement with Schering-Plough for Vtaribavirin in Japan. In exchange for the exclusive option, Schering- Plough has agreed to waive and release its last right of refusal on taribavirin under a 2000 agreement, providing more flexibility for Valeant to actively pursue partnering arrangements for the rest of the world. Under the terms of the option agreement, Valeant granted Schering- Plough the option to enter into an exclusive license agreement for the development and commercialization of taribavirin in Japan. Upon exercising the option and entering into the exclusive license agreement, Schering-Plough would provide a $2 million upfront payment to Valeant and pay mid-single digit royalties on net sales of taribavirin in Japan. Taribavirin, a prodrug of ribavirin, is in Phase II development for the treatment of chronic hepatitis C in conjunction with a pegylated interferon. “This agreement with Schering-Plough releases our company from the last right of refusal and provides us more flexibility to pursue partnering opportunities with other companies,” said J. Michael Pearson, Valeant’s chairman and chief executive officer. “With the data we have seen so far from the Phase IIb trial, we believe that taribavirin presents an attractive licensing opportunity.” About Taribavirin Taribavirin is an investigational compound that has not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory agency for the diagnosis, mitigation, treatment or cure of any disease or illness.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Repurposing of FDA Approved Drugs
    Antiviral Drugs (In Phase IV) ABACAVIR GEMCITABINE ABACAVIR SULFATE GEMCITABINE HYDROCHLORIDE ACYCLOVIR GLECAPREVIR ACYCLOVIR SODIUM GRAZOPREVIR ADEFOVIR DIPIVOXIL IDOXURIDINE AMANTADINE IMIQUIMOD AMANTADINE HYDROCHLORIDE INDINAVIR AMPRENAVIR INDINAVIR SULFATE ATAZANAVIR LAMIVUDINE ATAZANAVIR SULFATE LEDIPASVIR BALOXAVIR MARBOXIL LETERMOVIR BICTEGRAVIR LOPINAVIR BICTEGRAVIR SODIUM MARAVIROC BOCEPREVIR MEMANTINE CAPECITABINE MEMANTINE HYDROCHLORIDE CARBARIL NELFINAVIR CIDOFOVIR NELFINAVIR MESYLATE CYTARABINE NEVIRAPINE DACLATASVIR OMBITASVIR DACLATASVIR DIHYDROCHLORIDE OSELTAMIVIR DARUNAVIR OSELTAMIVIR PHOSPHATE DARUNAVIR ETHANOLATE PARITAPREVIR DASABUVIR PENCICLOVIR DASABUVIR SODIUM PERAMIVIR DECITABINE PERAMIVIR DELAVIRDINE PIBRENTASVIR DELAVIRDINE MESYLATE PODOFILOX DIDANOSINE RALTEGRAVIR DOCOSANOL RALTEGRAVIR POTASSIUM DOLUTEGRAVIR RIBAVIRIN DOLUTEGRAVIR SODIUM RILPIVIRINE DORAVIRINE RILPIVIRINE HYDROCHLORIDE EFAVIRENZ RIMANTADINE ELBASVIR RIMANTADINE HYDROCHLORIDE ELVITEGRAVIR RITONAVIR EMTRICITABINE SAQUINAVIR ENTECAVIR SAQUINAVIR MESYLATE ETRAVIRINE SIMEPREVIR FAMCICLOVIR SIMEPREVIR SODIUM FLOXURIDINE SOFOSBUVIR FOSAMPRENAVIR SORIVUDINE FOSAMPRENAVIR CALCIUM STAVUDINE FOSCARNET TECOVIRIMAT FOSCARNET SODIUM TELBIVUDINE GANCICLOVIR TENOFOVIR ALAFENAMIDE GANCICLOVIR SODIUM TENOFOVIR ALAFENAMIDE FUMARATE TIPRANAVIR VELPATASVIR TRIFLURIDINE VIDARABINE VALACYCLOVIR VOXILAPREVIR VALACYCLOVIR HYDROCHLORIDE ZALCITABINE VALGANCICLOVIR ZANAMIVIR VALGANCICLOVIR HYDROCHLORIDE ZIDOVUDINE Antiviral Drugs (In Phase III) ADEFOVIR LANINAMIVIR OCTANOATE
    [Show full text]
  • 1 Identification of Potent Drugs and Antiviral Agents for the Treatment Of
    1 Identification of Potent Drugs and Antiviral Agents for the Treatment of the SARS- CoV-2 Infection N.R. Jena* Discipline of Natural Sciences, Indian Institute of Information Technology, Design, and Manufacturing Dumna Airport Road, Jabalpur-482005, India *Corresponding author’s email address: [email protected] Abstract The recent outbreak of the SARS-CoV-2 infection has affected the lives and economy of more than 200 countries. The unavailability of vaccines and the virus-specific drugs has created an opportunity to repurpose existing drugs to examine their efficacy in controlling the virus activities. Here, the inhibition of the RdRp viral protein responsible for the replication of the virus in host cells is examined by evaluating the binding patterns of various approved and investigational antiviral, antibacterial, and anti-cancer drugs by using the molecular docking approach. Some of these drugs have been proposed to be effective against the SARS- Cov-2 virus infection. In an attempt to discover new antiviral agents, artificially expanded genetic alphabets (AEGIS) such as dP, dZ, dJ, dV, dX, dK, dB, dS, dP4, and dZ5 and different sequences of these nucleotides were also docked into the active site of the RdRp protein. It is found that among the various approved and investigational drugs, the Clevudine, N4-hydroxycytidine (EIDD-1931), 2'-C-methylcytidine, EIDD-2801, Uprifosbuvir, Balapiravir, Acalabrutinib, BMS-986094, Remdesivir (full drug), GS-6620, and Ceforanide would act as potent inhibitors of the RdRp protein. Similarly, among the AEGIS nucleotides, dB, dJ, dP, dK, dS, dV, and dZ are found to inhibit the RdRp protein efficiently.
    [Show full text]
  • Graphical Deep Matrix Factorization for in Silico Antiviral Repositioning: Application to COVID-19
    DeepVir - Graphical Deep Matrix Factorization for In Silico Antiviral Repositioning: Application to COVID-19 Aanchal Mongia1, Stuti Jain3, Emilie Chouzenoux2∗ & Angshul Majumdar3∗ 1Dept. of CSE, IIIT - Delhi, India, 110020 2CVN, Inria Saclay, Univ. Paris Saclay, 91190 Gif-sur-Yvette, France 3Dept. of ECE, IIIT - Delhi, India, 110020 ∗Corresponding authors contact/Email: [email protected], [email protected] September 23, 2020 Abstract This work formulates antiviral repositioning as a matrix completion problem where the antiviral drugs are along the rows and the viruses along the columns. The input matrix is partially filled, with ones in positions where the antiviral has been known to be effective against a virus. The curated metadata for antivirals (chemical structure and pathways) and viruses (genomic structure and symptoms) is encoded into our matrix completion framework as graph Laplacian regularization. We then frame the resulting multiple graph regularized matrix completion problem as deep matrix factorization. This is solved by using a novel optimization method called HyPALM (Hybrid Proximal Alternating Linearized Minimization). Results on our curated RNA drug virus association (DVA) dataset shows that the proposed approach excels over state-of-the-art graph regularized matrix completion techniques. When applied to in silico prediction of antivirals for COVID-19, our approach returns antivirals that are either used for treating patients or are under for trials for the same. Contact: [email protected] 1 Introduction The problem of matrix completion has been deployed in numerous applications of computer science and bioinfor- matics. One can mention, for instance, recommender systems [13], wireless sensor networks [12] and MIMO channel estimation [73].
    [Show full text]