Dual docking of some synthesized isoxazolidine derivatives against Cathepsin L and main protease as a novel treatment strategy for COVID-19

Abstract

Coronavirus disease 19 (COVID-19) continues to form a stressful threat to various sectors worldwide. With the advent of a new wave of Omicron sub-variant, exploration of novel drugs and strategies to cure COVID-19 patients are highly demanded. The current study evaluates the druggability of synthesized isoxazolidine derivatives(a, b) which are characterized by FT-IR, 13C NMR, and 1H NMR spectroscopy against cathepsin L and main protease (Mpro) using molecular docking. Procathepsin L 3D structure was predicted using SwissModel and then refined utilizing Galaxyrefine server. The refined structure in addition to MPpro retrieved from PDB served as receptors for docking by isoxazolidine derivatives using CB-Dock 2 and SwissDock platforms. Besides, drug-likeness and toxicity issues of the tested ligands were predicted using ADMET lab 2 and ProTox-II web servers. Molecular dynamics was conducted through Visual Dynamics server. Isoxazolidine derivatives exhibited strong dual inhibitory activity toward both receptors as well as good pharmacokinetics parameters. The tested ligands are a superior therapy option toward COVID-19.