AUTHOR=Sankar Muthumanickam , Ramachandran Balajee , Pandi Boomi , Mutharasappan Nachiappan , Ramasamy Vidhyavathi , Prabu Poorani Gurumallesh , Shanmugaraj Gowrishankar , Wang Yao , Muniyandai Brintha , Rathinasamy Subaskumar , Chandrasekaran Balakumar , Bayan Mohammad F. , Jeyaraman Jeyakanthan , Halliah Gurumallesh Prabu , Ebenezer Solomon King TITLE=In silico Screening of Natural Phytocompounds Towards Identification of Potential Lead Compounds to Treat COVID-19 JOURNAL=Frontiers in Molecular Biosciences VOLUME=8 YEAR=2021 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.637122 DOI=10.3389/fmolb.2021.637122 ISSN=2296-889X ABSTRACT=

COVID-19 is one of the members of the coronavirus family that can easily assail humans. As of now, 10 million people are infected and above two million people have died from COVID-19 globally. Over the past year, several researchers have made essential advances in discovering potential drugs. Up to now, no efficient drugs are available on the market. The present study aims to identify the potent phytocompounds from different medicinal plants (Zingiber officinale, Cuminum cyminum, Piper nigrum, Curcuma longa, and Allium sativum). In total, 227 phytocompounds were identified and screened against the proteins S-ACE2 and Mpro through structure-based virtual screening approaches. Based on the binding affinity score, 30 active phytocompounds were selected. Amongst, the binding affinity for beta-sitosterol and beta-elemene against S-ACE2 showed −12.0 and −10.9 kcal/mol, respectively. Meanwhile, the binding affinity for beta-sitosterol and beta-chlorogenin against Mpro was found to be −9.7 and −8.4 kcal/mol, respectively. Further, the selected compounds proceeded with molecular dynamics simulation, prime MM-GBSA analysis, and ADME/T property checks to understand the stability, interaction, conformational changes, binding free energy, and pharmaceutical relevant parameters. Moreover, the hotspot residues such as Lys31 and Lys353 for S-ACE2 and catalytic dyad His41 and Cys145 for Mpro were actively involved in the inhibition of viral entry. From the in silico analyses, we anticipate that this work could be valuable to ongoing novel drug discovery with potential treatment for COVID-19.