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?:abstract
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Recently, the emergence and dissemination of SARS-CoV-2 has caused high mortality and enormous economic loss In the fight against COVID-19, the rapid development of new drug molecules is the need of hour However, the conventional approaches of drug development is time consuming and costly in nature In this study, we have adopted an alternative approach to identify lead molecules from natural sources using high throughput virtual screening approach Ligands from natural compounds library from Selleck Inc (L1400) have been screened to evaluate their ability to bind and inhibit the main protease (Msuppro/suor 3CLsuppro/sup) of SARS-CoV-2, which is a potential drug target We found that Kaempferol, Quercetin, and Rutin were able to bind at the substrate binding pocket of 3CLsuppro/suwith high affinity (10sup5/sup-10sup6/suMsup-1/sup) and interact with the active site residues such as His41 and Cys145 through hydrogen bonding and hydrophobic interactions In fact, the binding affinity of Rutin was much higher than Chloroquine (1000 times) and Hydroxychloroquine (100 times) and was comparable to that of the reference drug Remdesivir, which is in clinical trials to treat COVID-19 patients The results suggest the potential of natural compounds (flavonoids) as novel inhibitors of SARS-CoV-2 with comparable potency as that of Remdesivir
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The emergence and dissemination of SARS-CoV-2 has caused high mortality and enormous economic loss. Rapid development of new drug molecules is the need of hour to fight COVID-19. However, the conventional approaches of drug development are time consuming and expensive. Here, we have adopted a computational approach to identify lead molecules from nature. Ligands from natural compounds library available at Selleck Inc (L1400) have been screened for their ability to bind and inhibit the main protease (3CLpro) of SARS-CoV-2. We found that Kaempferol, Quercetin, and Rutin were bound at the substrate binding pocket of 3CLpro with high affinity (105-106 M-1) and interact with the active site residues such as His41 and Cys145 through hydrogen bonding and hydrophobic interactions. In fact, the binding affinity of Rutin (~106 M-1) was much higher than Chloroquine (~103 M-1) and Hydroxychloroquine (~104 M-1), and the reference drug Remdesivir (~105 M-1). The results suggest that natural compounds such as flavonoids have the potential to be developed as novel inhibitors of SARS-CoV-2 with a comparable/higher potency as that of Remdesivir. However, their clinical usage on COVID-19 patients is a subject of further investigations and clinical trials.
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