Diversifying the chloroquinoline scaffold against SARS-COV-2 main protease: Virtual screening approach using cross-docking, sitemap analysis and molecular dynamics simulation

The absence of designated remedies for coronavirus disease 19 (Covid-19) and the lack treatment protocols drove scientists to propose new small molecules attempt repurpose existing drugs against various targets severe acute respiratory syndrome 2 (SARS-CoV-2) in order bring forward efficient solutions. main protease (Mpro) is one most promising drug due its crucial role fighting viral replication. Several antiviral have been used an overcome pandemic, such as hydroxychloroquine (HCQ). Despite perceived positive outcomes beginning disease, HCQ was associated with several drawbacks, insolubility, toxicity, cardiac adverse effects. Therefore, present study, a structure-based virtual screening approach performed identify structurally modified ligands chloroquinoline (CQ) scaffold good solubility, absorption, permeation aimed at eventually suggesting more dependable alternative. PDB ID:7BRP Mpro chosen reliable receptor after cross-docking calculation using 30 crystal structures. Then, SiteMap analysis total 231,456 compounds CQ were suggested. After Lipinski criteria filtration, 64,312 docked their MM-GBSA free binding energy calculated. Next, ADME descriptors calculated, 12 properties better than that identified. resulting subjected molecular dynamics (MD) simulation 100 ns. results study indicate 3 (CQ_22; CQ_2 CQ_5) show interactions stability receptor. Binding interaction indicates GLU143, THR26, HIS41 amino acids are potential hot-spot residues remaining ligands.