The continuous spread and evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the rapid surge in infection cases in the coronavirus disease 2019 (COVID-19) evoke a dire need for effective therapeutics. In this study, we explored the inhibitory potential of a library of 605 phytocompounds, selected from Indian medicinal plants with reported antiviral and anti-inflammatory activities, against the receptor-binding domain of spike proteins of the SARS-CoV-2 wild-type and the variants of concern, including variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Our approach was based on extensive molecular docking, assessment of drug-likeness, and robust molecular dynamics simulations. We also identified promising inhibitory candidates against the host (human) proteins associated with SARS-CoV-2 spike activation and attachment, namely, ACE2 receptor, proteases TMPRSS2 and CTSL, and the endocytic regulator AAK1. In addition, we screened promising inhibitory compounds against the human proinflammatory cytokines- IL-6, IL-1β, TNF-α, and IFN-γ, that are associated with the adverse cytokine storm in COVID-19 patients. Our analysis returned an encouraging list of promising inhibitory candidates that includes: abietatriene against the spike proteins of the SARS-CoV-2 wild-type and the variants of concern; taraxerol against the human ACE2, CTSL and TNF-α; β-amyrin against the human TMPRSS2; cynaroside against the human AAK1 and IL-1β; and friedelin against the human IL-6 and IFN-γ. Our findings provide substantial evidence for the inhibitory potential of these compounds and encourage further in vitro and in vivo studies to validate their use as safe and effective therapeutics against COVID-19.
|Journal||Journal of Cellular Biochemistry|
|Early online date||27 Mar 2022|
|Publication status||E-pub ahead of print - 27 Mar 2022|
Bibliographical noteFunding Information:
Md. Moshfekus Saleh‐E‐In and Yong E. Choi acknowledge Brain Pool Program through the National Research Foundation of Korea (NRF) for the work (Grant number: 2019H1D3A1A01071150). Nishika Jaishee, Akash Anandraj, Emil Kormuth, and Devashan Naidoo are thankful to the Mangosuthu University of Technology, South Africa for the infrastructure facility.
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