Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach
| Autor: | Naif Abdullah Al-Dhabi, Mariadhas Valan Arasu, Narasingam Arunagirinathan, Purushothaman Indu, Marimuthu Ragavan Rameshkumar, Savarimuthu Ignacimuthu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pyridines Etravirine Indinavir Pharmacology RNA-dependent RNA polymerase Piperazines chemistry.chemical_compound 0302 clinical medicine 030212 general & internal medicine Sulfonamides Chemistry lcsh:Public aspects of medicine RNA dependent RNA polymerase General Medicine Pibrentasvir Molecular Docking Simulation Coronavirus Protease Inhibitors Infectious Diseases docking Dolutegravir Heterocyclic Compounds 3-Ring Tipranavir medicine.drug Pyridones medicine.drug_class 030106 microbiology Antiviral Agents Article lcsh:Infectious and parasitic diseases antiviral drugs 03 medical and health sciences Raltegravir Potassium Nitriles Oxazines medicine Humans lcsh:RC109-216 SARS-CoV-2 Drug Repositioning Public Health Environmental and Occupational Health COVID-19 lcsh:RA1-1270 Glecaprevir Raltegravir COVID-19 Drug Treatment Pyrimidines Pyrones main protease Antiviral drug |
| Zdroj: | Journal of Infection and Public Health Journal of Infection and Public Health, Vol 13, Iss 12, Pp 1856-1861 (2020) |
| ISSN: | 1876-0341 |
| DOI: | 10.1016/j.jiph.2020.10.015 |
| Popis: | Background Outbreak of COVID-19 has been recognized as a global health concern since it causes high rates of morbidity and mortality. No specific antiviral drugs are available for the treatment of COVID-19 till date. Drug repurposing strategy helps to find out the drugs for COVID-19 treatment from existing FDA approved antiviral drugs. In this study, FDA approved small molecule antiviral drugs were repurposed against the major viral proteins of SARS-CoV-2. Methods The 3D structures of FDA approved small molecule antiviral drugs were retrieved from PubChem. Virtual screening was performed to find out the lead antiviral drug molecules against main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) using COVID-19 Docking Server. Furthermore, lead molecules were individually docked against protein targets using AutoDock 4.0.1 software and their drug-likeness and ADMET properties were evaluated. Results Out of 65 FDA approved small molecule antiviral drugs screened, Raltegravir showed highest interaction energy value of -9 kcal/mol against Mpro of SARS-CoV-2 and Indinavir, Tipranavir, and Pibrentasvir exhibited a binding energy value of ≥−8 kcal/mol. Similarly Indinavir showed the highest binding energy of -11.5 kcal/mol against the target protein RdRp and Dolutegravir, Elbasvir, Tipranavir, Taltegravir, Grazoprevir, Daclatasvir, Glecaprevir, Ledipasvir, Pibrentasvir and Velpatasvir showed a binding energy value in range from -8 to -11.2 kcal/mol. The antiviral drugs Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine also exhibited good bioavailability and drug-likeness properties. Conclusion This study suggests that the screened small molecule antiviral drugs Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine could serve as potential drugs for the treatment of COVID-19 with further validation studies. |
| Databáze: | OpenAIRE |
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