Abstract 712: Anticancer natural compounds as potential inhibitors of novel coronavirus (COVID19) main protease: An in-silico study
Authors: Mishra Amaresh , Pathak Yamini , Choudhir Gourav , Kumar Anuj , Mishra Surabhi Kirti , Tripathi Vishwas 
Published: July 2021

Abstract
Introduction: Severe acute respiratory syndrome coronavirus identified as the root cause of the Coronavirus disease 2019 (COVID-19) has spread all over the world. The pandemic situation caused by SARS-CoV-2 currently challenging the world. Given that the COVID-19 disease has no vaccine or therapeutic drugs to prevent the infection. In contrast, the key protease (Mpro) of SARS CoV-2 is involved in replication and proliferation of the virus and hence represents a crucial drug for the inhibition of COVID-19. Recent development shows the antiviral and anti-cancerous potential of natural products in the drug development process against various diseases which resulted in the screening of such agents to combat emergent mutants of SARS-CoV-2. Herein, we have applied a bioinformatics approach including molecular docking and a combination of molecular dynamics simulations and Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations to identify the inhibitory potency of candidates against SARS-CoV2 main protease. Methods: In-Silico molecular docking analysis was performed for all selected anti-cancerous natural compounds with the potential drug target, PDB Id: 6W63 COVID-19 main protease in complex with a noncovalent inhibitor X77 using molecular docking and a combination of molecular dynamics simulations and Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations. Absorption, Distribution, Metabolism, and Excretion (ADME) property as well as Lipinski's rule of five was also predicted for all the selected compounds. Among the 20 natural compounds, four natural metabolites namely, amentoflavone, guggulsterone, puerarin, and piperine were found to have strong interaction with Mpro of COVID-19. During MD simulations, all four natural compounds bound to Mpro at 50ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands have stable and favorable energies causing strong binding with the binding site of Mpro protein.
Conclusion: Although the anti-cancerous natural compounds show high binding affinity with the active site of SARS-CoV-2 main protease. Among these Amentoflavone and Guggulsterone were the top two leads showing the lowest binding energy and satisfying our studied parameters. Guggulsterone of Indian traditional ayurvedic medical plant Commiphoramukul was found to be the most suitable based on comprehensive pharmacokinetic parameters, drug-likeness, and docking analysis. Therefore, we propose anti-cancerous natural compound Guggulsterone may further be validated as potential inhibitors of COVID-19 main protease Mpro.
Citation Format: Amaresh Mishra, Yamini Pathak, Gourav Choudhir, Anuj Kumar, Surabhi Kirti Mishra, Vishwas Tripathi. Anticancer natural compounds as potential inhibitors of novel coronavirus (COVID19) main protease: An in-silico study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 712.