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
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Journal of Infection and Public Health |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1876034120307127 |
| _version_ | 1819056580027482112 |
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| author | Purushothaman Indu Marimuthu Ragavan Rameshkumar Narasingam Arunagirinathan Naif Abdullah Al-Dhabi Mariadhas Valan Arasu Savarimuthu Ignacimuthu |
| author_facet | Purushothaman Indu Marimuthu Ragavan Rameshkumar Narasingam Arunagirinathan Naif Abdullah Al-Dhabi Mariadhas Valan Arasu Savarimuthu Ignacimuthu |
| author_sort | Purushothaman Indu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T13:25:40Z |
| format | Article |
| id | doaj.art-5fa0ff3cd7384d479e91c1f47a351e93 |
| institution | Directory Open Access Journal |
| issn | 1876-0341 |
| language | English |
| last_indexed | 2024-12-21T13:25:40Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Infection and Public Health |
| spelling | doaj.art-5fa0ff3cd7384d479e91c1f47a351e932022-12-21T19:02:28ZengElsevierJournal of Infection and Public Health1876-03412020-12-01131218561861Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approachPurushothaman Indu0Marimuthu Ragavan Rameshkumar1Narasingam Arunagirinathan2Naif Abdullah Al-Dhabi3Mariadhas Valan Arasu4Savarimuthu Ignacimuthu5Department of Microbiology and Biotechnology, Presidency College (Autonomous), Affiliated to University of Madras, Chennai, IndiaLaboratory Division, ICMR-National Institute of Epidemiology, Chennai, India; Corresponding author.Department of Microbiology and Biotechnology, Presidency College (Autonomous), Affiliated to University of Madras, Chennai, India; Central Research Laboratory, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, IndiaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; Xavier Research Foundation, St. Xavier’s College, Palayamkottai, Thirunelveli, Tamilandu, IndiaXavier Research Foundation, St. Xavier’s College, Palayamkottai, Thirunelveli, Tamilandu, IndiaBackground: 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.http://www.sciencedirect.com/science/article/pii/S1876034120307127COVID-19SARS-CoV-2Main proteaseRNA-dependent RNA polymeraseAntiviral drugsDocking |
| spellingShingle | Purushothaman Indu Marimuthu Ragavan Rameshkumar Narasingam Arunagirinathan Naif Abdullah Al-Dhabi Mariadhas Valan Arasu Savarimuthu Ignacimuthu 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 Journal of Infection and Public Health COVID-19 SARS-CoV-2 Main protease RNA-dependent RNA polymerase Antiviral drugs Docking |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | COVID-19 SARS-CoV-2 Main protease RNA-dependent RNA polymerase Antiviral drugs Docking |
| url | http://www.sciencedirect.com/science/article/pii/S1876034120307127 |
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