Targeting SARS-CoV-2 Main Protease by Teicoplanin: A Mechanistic Insight by in Silico Studies

First emerged in late December 2019, the outbreak of novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic has instigated public-health emergency around the globe. Although available medications can only alleviate few symptoms like difficulty in breathing, the world is craving to identify specific antiviral agents or vaccines against SARS-CoV-2. Teicoplanin is a glycopeptide class of antibiotic which is regularly used for treating Gram-positive bacterial infections, has shown potential therapeutic efficacy against SARS-CoV-2 in vitro. Therefore, in this study, a mechanistic insight of intermolecular interactions between teicoplanin and SARS-CoV-2 main protease has been scrutinized by employing molecular modelling approaches. Molecular docking study was carried out by three different docking programs including AutoDock4, AutoDock Vina and Dock6. The dynamic and thermodynamics constraints of docked drug in complex with target protein under specific physiological conditions was ascertained by all-atom molecular dynamics (MD) simulation study. Root mean square deviation of carbon α chain exhibited uniform value in the range of 1-1.7 Å while root mean square fluctuations were also recorded below 1.72 Å, justifying the stability of the bound complex in biological environments. Key interacting residues involved in hydrogen bonds include Thr26, His41, Asn142, Ser144, Glu166, and Gln189. Several water bridges and hydrophobic interactions also anchored docked teicoplanin in the inhibitor binding site. These outcomes are supposed to be fruitful in rational design of antiviral drugs against SARS-CoV-2.