| Autor: |
Abo Elmaaty A; Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt., Hamed MIA; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt., Ismail MI; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, Cairo-Suez Desert Road, Cairo 11837, Egypt., B Elkaeed E; Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah, Riyadh 13713, Saudi Arabia.; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo 11884, Egypt., S Abulkhair H; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo 11884, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt., Khattab M; Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo 12622, Egypt., Al-Karmalawy AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt. |
| Abstrakt: |
The discovery of drugs capable of inhibiting SARS-CoV-2 is a priority for human beings due to the severity of the global health pandemic caused by COVID-19. To this end, repurposing of FDA-approved drugs such as NSAIDs against COVID-19 can provide therapeutic alternatives that could be utilized as an effective safe treatment for COVID-19. The anti-inflammatory activity of NSAIDs is also advantageous in the treatment of COVID-19, as it was found that SARS-CoV-2 is responsible for provoking inflammatory cytokine storms resulting in lung damage. In this study, 40 FDA-approved NSAIDs were evaluated through molecular docking against the main protease of SARS-CoV-2. Among the tested compounds, sulfinpyrazone 2 , indomethacin 3 , and auranofin 4 were proposed as potential antagonists of COVID-19 main protease. Molecular dynamics simulations were also carried out for the most promising members of the screened NSAID candidates ( 2 , 3 , and 4 ) to unravel the dynamic properties of NSAIDs at the target receptor. The conducted quantum mechanical study revealed that the hybrid functional B3PW91 provides a good description of the spatial parameters of auranofin 4 . Interestingly, a promising structure-activity relationship (SAR) was concluded from our study that could help in the future design of potential SARS-CoV-2 main protease inhibitors with expected anti-inflammatory effects as well. NSAIDs may be used by medicinal chemists as lead compounds for the development of potent SARS-CoV-2 (M pro ) inhibitors. In addition, some NSAIDs can be selectively designated for treatment of inflammation resulting from COVID-19. |
