Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking
Abstract Background: COVID-19 (Coronavirus disease 2019) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which poses significant global health and economic crisis that urges effective treatment. Methods: A total of 11 molecules (baricitinib, danoprevir, dexamethas...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Knowledge E
2022-09-01
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| Series: | Sudan Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.18502/sjms.v17i3.12125 |
| _version_ | 1811229256680734720 |
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| author | Yow Hui Yin Tang Yin-Quan |
| author_facet | Yow Hui Yin Tang Yin-Quan |
| author_sort | Yow Hui Yin |
| collection | DOAJ |
| description | Abstract Background: COVID-19 (Coronavirus disease 2019) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which poses significant global health and economic crisis that urges effective treatment. Methods: A total of 11 molecules (baricitinib, danoprevir, dexamethasone, hydroxychloroquine, ivermectin, lopinavir, methylprednisolone, remdesivir, ritonavir and saridegib, ascorbic acid, and cepharanthine) were selected for molecular docking studies using AutoDock VINA to study their antiviral activities via targeting SARS-CoV's main protease (Mpro), a cysteine protease that mediates the maturation cleavage of polyproteins during virus replication. Results: Three drugs showed stronger binding affinity toward Mpro than N3 (active Mpro inhibitor as control): danoprevir (–7.7 kcal/mol), remdesivir (–8.1 kcal/mol), and saridegib (–7.8 kcal/mol). Two primary conventional hydrogen bonds were identified in the danoprevir-Mpro complex at GlyA:143 and GlnA:189, whereas the residue GluA:166 formed a carbon–hydrogen bond. Seven main conventional hydrogen bonds were identified in the remdesivir at AsnA:142, SerA:144, CysA:145, HisA:163, GluA:166, and GlnA:189, whereas two carbon–hydrogen bonds were formed by the residues HisA:41 and MetA:165. Cepharanthine showed a better binding affinity toward Mpro (–7.9 kcal/mol) than ascorbic acid (–5.4 kcal/mol). Four carbon–hydrogen bonds were formed in the cepharanthine-Mpro complex at HisA:164, ProA;168, GlnA;189, and ThrA:190. Conclusion: The findings of this study propose that these drugs are potentially inhibiting the SAR-CoV-2 virus by targeting the Mpro protein. |
| first_indexed | 2024-04-12T10:11:31Z |
| format | Article |
| id | doaj.art-bc95a5236cf0413d8819365de91335a3 |
| institution | Directory Open Access Journal |
| issn | 1858-5051 |
| language | English |
| last_indexed | 2024-04-12T10:11:31Z |
| publishDate | 2022-09-01 |
| publisher | Knowledge E |
| record_format | Article |
| series | Sudan Journal of Medical Sciences |
| spelling | doaj.art-bc95a5236cf0413d8819365de91335a32022-12-22T03:37:18ZengKnowledge ESudan Journal of Medical Sciences1858-50512022-09-0117339841110.18502/sjms.v17i3.12125sjms.v17i3.12125Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular DockingYow Hui Yin0Tang Yin-Quan1 School of Pharmacy, Faculty of Health and Medical Sciences Taylor's University, Subang Jaya, Malaysia Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, MalaysiaAbstract Background: COVID-19 (Coronavirus disease 2019) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which poses significant global health and economic crisis that urges effective treatment. Methods: A total of 11 molecules (baricitinib, danoprevir, dexamethasone, hydroxychloroquine, ivermectin, lopinavir, methylprednisolone, remdesivir, ritonavir and saridegib, ascorbic acid, and cepharanthine) were selected for molecular docking studies using AutoDock VINA to study their antiviral activities via targeting SARS-CoV's main protease (Mpro), a cysteine protease that mediates the maturation cleavage of polyproteins during virus replication. Results: Three drugs showed stronger binding affinity toward Mpro than N3 (active Mpro inhibitor as control): danoprevir (–7.7 kcal/mol), remdesivir (–8.1 kcal/mol), and saridegib (–7.8 kcal/mol). Two primary conventional hydrogen bonds were identified in the danoprevir-Mpro complex at GlyA:143 and GlnA:189, whereas the residue GluA:166 formed a carbon–hydrogen bond. Seven main conventional hydrogen bonds were identified in the remdesivir at AsnA:142, SerA:144, CysA:145, HisA:163, GluA:166, and GlnA:189, whereas two carbon–hydrogen bonds were formed by the residues HisA:41 and MetA:165. Cepharanthine showed a better binding affinity toward Mpro (–7.9 kcal/mol) than ascorbic acid (–5.4 kcal/mol). Four carbon–hydrogen bonds were formed in the cepharanthine-Mpro complex at HisA:164, ProA;168, GlnA;189, and ThrA:190. Conclusion: The findings of this study propose that these drugs are potentially inhibiting the SAR-CoV-2 virus by targeting the Mpro protein.https://doi.org/10.18502/sjms.v17i3.12125repurposed drug, covid-19, mpro, docking |
| spellingShingle | Yow Hui Yin Tang Yin-Quan Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking Sudan Journal of Medical Sciences repurposed drug, covid-19, mpro, docking |
| title | Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking |
| title_full | Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking |
| title_fullStr | Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking |
| title_full_unstemmed | Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking |
| title_short | Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking |
| title_sort | computational screening of repurposed drugs targeting sars cov 2 main protease by molecular docking |
| topic | repurposed drug, covid-19, mpro, docking |
| url | https://doi.org/10.18502/sjms.v17i3.12125 |
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