Identification of inhibitory activities of Thearubigin Analogues Against SARS-Corovirus-2 Non-Structural Protein 10-16 complex: A Computational Drug Designing approach

The frequent mutation capacity of SARS-CoV-2 and lack of effective therapy methods have put the world on high alert. In this work, novel compound searching was carried out for SARS-CoV-2 protein showing low mutation susceptibility. The probability of undergoing viral escape mutation to the effects of drug is lower if conserved proteins are targeted by drugs. Mutation rate analysis of all SARS-CoV-2 proteins was carried out to identify proteins which are less mutation prone. Because thearubigin was discovered to have inhibitory effects against viral 3-chymotrypsin-like-proteases involved in coronavirus replication, virtual screening method was used to look for chemicals with similar structures to thearubigin that could have effects against SARS-CoV-2 NSP10-16 complex. Out of 1000 compounds having thearubigin-like structures located using PubChem, 31 were filtered out using Lipinski's rule of five. ADMET profiling, molecular docking, and molecular dynamics simulation investigations of hit compounds were carried out. Four compounds (PubChem IDs 90950326, 54764514, 124086159, and 122450369) showed probable molecular interactions with NSP10-16 after docking experiments. Furthermore, molecular dynamics simulations were run for 100 ns to determine SASA, RMSD, RMSF, and Rg values of thearubigin and hits in order to reveal the binding kinetics, structural behavior, and flexibility of these compounds. All ligands exhibit drug-like qualities and can be subjected to further lead optimization in order to be produced as medications. The absorption profiles of the hit ligands were analyzed computationally in human models using GastroPlus software. This research adds to the body of knowledge and guidelines for developing effective SARS-CoV-2 treatments.