Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking

Abstract

Background: 2019-nCoV (COVID-19) is a pandemic disease with a high infectivity and mortality. The prevention and treatment of COVID-19 have become urgent matters for consideration. It often takes several years to develop new drugs, or vaccines, based on the usual clinical trial process. This dwell-time can be shortened by repurposing previously approved drugs.Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase We aimed to assess several available small-molecule; Abl kinase inhibitors, Janus kinase inhibitor, Dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papin-like Protease inhibitors, using binding simulation with proteins that might prove to be effective in inhibiting COVID-19 infection. The efficiency of inhibitors was evaluated based on docking scores using auto dock vina software.Results: Strong ligand-protein interactions were predicted among some of these drugs, such as Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control (directly and indirectly) or in viral proteins attenuation. It is worth to highlight the powerful immunomodulatory role of Abivertinib that inhibits pro-inflammatory cytokine production that are associated with cytokine release syndrome (CRS) or cytokine storm and progression of COVID-19 infection.Conclusions: COVID-19 is similar to SARS-CoV, the potential role of Abl kinase inhibitors such as Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS) may indicate that these drugs may be useful for COVID-19. Moreover, Remdesivir, and Telaprevir have the most efficiency with their docked proteins in-silico as well although clinical trials are needed to confirm the effect of these drugs.

Targeting human thymidylate synthase: Ensemble-based virtual screening for drug repositioning and the role of water

“…The pharmacokinetic pro le such as its oral bioavailability at 98%, and its tolerability make Imatinib an attractive candidate to reposition. It is therefore, not surprising that Imatinib has been studied for drug repositioning for several therapeutic targets and diseases [96][97][98][99][100][101][102][103][104]. In addition, due to its ability to cross the blood brain barrier, Imatinib presented an excellent choice of an approved drug to repurpose for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) [105].…”