Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular Docking
Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness unknown to a human before. Its alarmingly quick transmission to many countries across the world has resulted in a global health emergency. Therefore, an imminent need for drugs to combat this disease has been increased...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tabriz University of Medical Sciences
2021-11-01
|
| Series: | Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://ps.tbzmed.ac.ir/PDF/ps-27-S135.pdf |
| _version_ | 1819031845794217984 |
|---|---|
| author | Marzieh Omrani Mohammad Bayati Parvaneh Mehrbod Kamal Asmari Bardazard Samad Nejad-Ebrahimi |
| author_facet | Marzieh Omrani Mohammad Bayati Parvaneh Mehrbod Kamal Asmari Bardazard Samad Nejad-Ebrahimi |
| author_sort | Marzieh Omrani |
| collection | DOAJ |
| description | Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness unknown to a human before. Its alarmingly quick transmission to many countries across the world has resulted in a global health emergency. Therefore, an imminent need for drugs to combat this disease has been increased. Worldwide collaborative efforts from scientists are underway to determine a therapy to treat COVID-19 infections and reduce mortality rates. Since herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs), this in silico evaluation was performed for identifying potential natural compounds with promising inhibitory activities against COVID-19. Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used asa fast method for discovering novel drug candidates as potential COVID-19 main protease(Mpro) inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINCdatabase and virtually screened against the COVID-19 Mpro. In this study, the Glide docking program was applied for high throughput virtual screening. Also, Extra precision (XP) has been used following the induced-fit docking (IFD) approach. The ADME properties of all compounds were analyzed and a final selection was made based on the Lipinski rule of five. Also, molecular dynamics (MD) simulations were conducted for a virtual complex of the best scoring compound with COVID-19 protease. Results: Nineteen compounds were introduced as new potential inhibitors. CompoundZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamideshowed a strong binding affinity (-11.5 kcal/mol) to the COVID-19 Mpro comparing to peramivir (-9.8 kcal/mol) as a positive control. Conclusion: Based on these findings, nineteen compounds were proposed as possible new COVID-19 inhibitors, of which ZINC08765174 had a high affinity to Mpro. Furthermore, the promising ADME properties of the selected compounds emphasize their potential as attractive candidates for the treatments of COVID-19. |
| first_indexed | 2024-12-21T06:52:32Z |
| format | Article |
| id | doaj.art-543f8fba4e1d42f0b55e2d251008e350 |
| institution | Directory Open Access Journal |
| issn | 2383-2886 |
| language | English |
| last_indexed | 2024-12-21T06:52:32Z |
| publishDate | 2021-11-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Pharmaceutical Sciences |
| spelling | doaj.art-543f8fba4e1d42f0b55e2d251008e3502022-12-21T19:12:26ZengTabriz University of Medical SciencesPharmaceutical Sciences2383-28862021-11-0127Covid-19S135S14810.34172/PS.2021.11ps-33848Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular DockingMarzieh Omrani0Mohammad Bayati1Parvaneh Mehrbod2Kamal Asmari Bardazard3Samad Nejad-Ebrahimi4Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran..Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran..Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran, Iran.Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran..Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran..Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness unknown to a human before. Its alarmingly quick transmission to many countries across the world has resulted in a global health emergency. Therefore, an imminent need for drugs to combat this disease has been increased. Worldwide collaborative efforts from scientists are underway to determine a therapy to treat COVID-19 infections and reduce mortality rates. Since herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs), this in silico evaluation was performed for identifying potential natural compounds with promising inhibitory activities against COVID-19. Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used asa fast method for discovering novel drug candidates as potential COVID-19 main protease(Mpro) inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINCdatabase and virtually screened against the COVID-19 Mpro. In this study, the Glide docking program was applied for high throughput virtual screening. Also, Extra precision (XP) has been used following the induced-fit docking (IFD) approach. The ADME properties of all compounds were analyzed and a final selection was made based on the Lipinski rule of five. Also, molecular dynamics (MD) simulations were conducted for a virtual complex of the best scoring compound with COVID-19 protease. Results: Nineteen compounds were introduced as new potential inhibitors. CompoundZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamideshowed a strong binding affinity (-11.5 kcal/mol) to the COVID-19 Mpro comparing to peramivir (-9.8 kcal/mol) as a positive control. Conclusion: Based on these findings, nineteen compounds were proposed as possible new COVID-19 inhibitors, of which ZINC08765174 had a high affinity to Mpro. Furthermore, the promising ADME properties of the selected compounds emphasize their potential as attractive candidates for the treatments of COVID-19.https://ps.tbzmed.ac.ir/PDF/ps-27-S135.pdfhtvsinduced-fit dockingmolecular modelingsars-covid-19 |
| spellingShingle | Marzieh Omrani Mohammad Bayati Parvaneh Mehrbod Kamal Asmari Bardazard Samad Nejad-Ebrahimi Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular Docking Pharmaceutical Sciences htvs induced-fit docking molecular modeling sars-covid-19 |
| title | Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular Docking |
| title_full | Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular Docking |
| title_fullStr | Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular Docking |
| title_full_unstemmed | Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular Docking |
| title_short | Natural Products as Inhibitors of COVID-19 Main Protease – A Virtual Screening by Molecular Docking |
| title_sort | natural products as inhibitors of covid 19 main protease a virtual screening by molecular docking |
| topic | htvs induced-fit docking molecular modeling sars-covid-19 |
| url | https://ps.tbzmed.ac.ir/PDF/ps-27-S135.pdf |
| work_keys_str_mv | AT marziehomrani naturalproductsasinhibitorsofcovid19mainproteaseavirtualscreeningbymoleculardocking AT mohammadbayati naturalproductsasinhibitorsofcovid19mainproteaseavirtualscreeningbymoleculardocking AT parvanehmehrbod naturalproductsasinhibitorsofcovid19mainproteaseavirtualscreeningbymoleculardocking AT kamalasmaribardazard naturalproductsasinhibitorsofcovid19mainproteaseavirtualscreeningbymoleculardocking AT samadnejadebrahimi naturalproductsasinhibitorsofcovid19mainproteaseavirtualscreeningbymoleculardocking |