Molecular dynamics simulation and docking studies reveal NF-κB as a promising therapeutic drug target for COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rampant worldwide and is a deadly disease for humans. Our current work emphasizes on molecular dynamics simulation (MDS) targeting nuclear factor-kappa B (NF-κB), the well-known human transcription factor controlling innate and adaptive immunity, to understand its mechanism of action during COVID-19 in humans. NF-κB was interacted with the SARS-CoV-2 spike protein in an in silico MDS experiment, revealing the NF-κB site at which the SARS-CoV-2 spike protein interacts. We screened some known drugs via docking studies on NF-κB used as a receptor. The MDS software Schrodinger generated more than 2000 complexes from these compounds and using the SMILES format of these complexes, 243 structures were extracted and 411 conformers were generated. The drug used as a ligand that docked with NF-κB with the best docking score and binding affinity was Sulindac sodium as its trade name. Furthermore, RMSF data of sulindac sodium and NF-κB displayed minimal fluctuations in the protein structures, and the protein-ligand complex had reduced flexibility. Sulindac sodium is hence suggested as a suitable drug candidate for repurposing in clinical trials for SARS-CoV-2 infections. This drug potently blocked the spike protein’s interaction with NF-κB by inducing a conformational change in the latter. Arguably, NF-κB inaction is desired to have normal immunity and can possibly be retained using proposed drug. This work provides a significant lead for drug repurposing to combat SARS-CoV-2 and its various mutant forms and reveals new approach for controlling SARS-CoV-2-induced disease.

In-Silico Screening and Molecular Dynamics Simulation of Drug Bank Experimental Compounds against SARS-CoV-2

“…The members of the coronaviridae family have caused various destruction earlier, and now one of its members has caused a global pandemic resulting in millions of deaths and a massive loss to various countries’ economic growth. This is all a result of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) [ 1 ]. It has crown-like spikes on the surface and belongs to the Coronaviridae family.…”

“…Despite the severity of the pandemic, there is no effective therapeutic available on the market. Scientists are working on drug repurposing or designing a novel candidate against SARS-CoV-2 to slow down infection and fatalities and take the world for positive development [ 1 ].…”