Computational Insights on the Potential of Some NSAIDs for Treating COVID-19: Priority Set and Lead Optimization

Molecules

Muhammad Khattab¹  Ayman Abo Elmaaty²  Mohammed I. A. Hamed³  Ahmed A. Al-Karmalawy⁴  Muhammad I. Ismail⁵  Eslam B. Elkaeed⁶  Hamada S. Abulkhair⁷ 

[1] Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo 12622, Egypt;Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt;Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, Cairo-Suez Desert Road, Cairo 11837, Egypt;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;

关键词: drug repurposing;    SARS-CoV-2 main protease;    docking;    molecular dynamics;    DFT calculations;   

DOI  :  10.3390/molecules26123772

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown