In silico molecular docking, dynamics simulation and repurposing of some VEGFR-2 inhibitors based on the SARS-CoV-2-main-protease inhibitor N3

Abstract

The global and rapid spread of the novel human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has brought immediate urgency to the discovery of favorable targets for COVID-19 treatment. Here, we consider drug reuse as an attractive methodology for drug discovery by reusing existing drugs to treat diseases other than their initial indications. Here, we review current information concerning the global health issue of COVID-19 including VEGFR-2 inhibitors. Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2. The present study suggests the potential anti-SARS-CoV-2 activities of 35 reported VEGFR-2 inhibitors containing the amide and urea linkers. Nineteen members revealed the best in silico results and hence, were subjected to further molecular dynamics (MD) simulation for their inhibitory activities against SARS-CoV-2 M^pro across 100 ns. Furthermore, MD simulations followed by calculations of the free energy of binding were also carried out for the most promising ligand-pocket complexes from docking studies to clarify some information on their dynamic and thermodynamic properties and approve the docking results. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• Drug repurposing
• thiazolidine-2,4-dined
• docking
• COVID-19
• main protease

Disclosure Statement

The authors declare no conflict of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.