Genistein demonstrates superb binding ability against Mpro: A Monte Carlo approach for developing novel SARS-CoV-2 inhibitors

Abstract

Abstract Background SARS-CoV-2, commonly known as the novel coronavirus or COVID-19, represents a highly contagious virus responsible for a global pandemic. Its suspected origin in bats led to its first identification in Wuhan, China, in late 2019. Primarily transmitted through respiratory droplets from infected individuals coughing or sneezing, the virus manifests symptoms such as fever, cough, and shortness of breath. Severe cases may escalate to pneumonia and respiratory failure. With a global death toll surpassing 6,937,771, the urgent quest for effective treatments continues. To address this critical need, our study systematically explores the computational screening of 52 flavonoids as potential SARS-CoV-2 inhibitors, emphasizing minimal adverse effects compared to conventional anti-viral drugs, which often present associated complications. Results Following the preparation of 58 ligands and the protein, a computational screening was conducted on flavonoids and standard drugs against the crystal structure of the SARS-CoV-2 Main Protease (7KYU) utilizing the virtual screening workflow (VSW) within Maestro 12.8 Schrodinger suite. Notably, only XC4, the co-ligand, and genistein successfully passed the VSW assessment. The selected ligands underwent additional screening processes, including PASS prediction, DFT, and ADMET profiling. Genistein exhibited superior results in terms of biological activity, binding energy, and binding free energy. The bioactivity scores further underscored the suitability of genistein for various biological functions. Conclusion The result of this study provide support for the refinement of genistein as a potential inhibitor for SARS-CoV-2. Consequently, we hold a favorable view of genistein.