Deciphering the impact of Mutations in the RBD of the Omicron Variant (BA.2) with Medicinal compound to disrupt the RBD-hACE2 complex using computational approaches

Abstract

Human health and the economy have been greatly affected by COVID-19 emergence, that originated from SARS-CoV-2. Just after the very first case of COVID-19 emerged, a number of variants have been reported with severe risk of reinfection and evading immunity. Overall, 30 mutations in the spike protein have been reported in SARS-CoV-2 (BA.2) variant in India and South Africa, while half among these 30 mutations are receptor-binding domain which have spread rapidly throughout the world. The modern world has been swaddled by this extremely contagious Omicron variant, while it is rapidly mutating that is alarming and need to be addressed. Due to antibodies-escaping activity, the micro molecule that can inhibit it, are required to be discovered. Therefore, we focused on the computational drug designing, including Pharmacophore based virtual Screening, MD simulation to identity the novel small molecular inhibitor that stop hACE2 to bind with Receptor Binding Domain (RBD). We screened three medicinal compound databases, North-East African, North African and East African We carried out a multi-step screening approach that identified three compounds, which are (10R)-3',4'-dihydro-1,4,8,3',8',9'-hexahydroxy-3,3-dimethyl-[10,7'-bianthracene]-9,1'(10H,2'H)-dione (C1), 6'-(4-hydroxy cinnamoyl) arbutin (C2), and Acacetin 7-glucoside (C3), that are effective for omicron RBD variant due its excellent antiviral capabilities. Then PAIN assay interference, computation bioactivity prediction, binding free energy and dissociation constant was used to validate the top hits, indicated the good anti-viral activity. To summarize, we aimed to identify and design novel medication therapies that could be utilized in combating with newly discovered omicron strain of SARS-CoV-2.