Modification of Remdesivir as a Better Inhibitor of COVID-19: A Computational Docking Study

Abstract

<div>Coronavirus (COVID-19) mediated infection is a highly contagious respiratory illness that was initially found in Wuhan city of Hubei Province in China. The ongoing pandemic of the novel SARS-CoV-2 virus is affecting global health. Despite the recent success in vaccination on a trial basis, there is no treatment of the infection. Thus, establishing an effective therapeutic measure is of apex priority among biologists and healthcare professionals. Re-purposing Remdesivir, a broad-spectrum antiviral agent that inhibits viral RNA polymerase, has been found effective for the treatment of COVID-19. In this study, modification of the existing drug Remdesivir was done. In logical drug designing and development, molecular recognition plays a central role in this sphere. The anti viral function of Remdesivir is achieved by binding to RNA polymerase enzyme. The protein 7BTF is an RNA-dependent RNA polymerase that plays a crucial role in coronavirus replication and transcription machinery and it appears to be the primary target of the antiviral drug Remdesivir. The study intend to design derivative compounds form Remdesivir to screen out the a better drug against the SARS-CoV-2 virus by inhibiting the targeted protein. The efficacy of these new drugs was also tested by molecular docking calculations. The drug derivatives were docked for binding affinity and non-bond interactions. Pharmacokinetic activities of the designed drugs are also predicted. All the drugs are non-carcinogenic and chemically reactive. In our study, modified compound D-I has exhibited the best performance among Remdesivir and it’s derivatives. This study might provide an insight into the potential of a Remdesivir derivative in treating SARS-CoV-2 infection<br></div>

Heterocyclic compounds as antiviral drugs: Synthesis, structure–activity relationship and traditional applications

“…The phosphoramidate group also improves cell membrane permeation [149]. Recent work in the literature suggests that remdesivir can be modified in the NH 2 group of the adenosine analogue, to enhance binding with viral proteins [150]. There is also some works suggesting modifications in the ester alkyl group to enhance protein binding [151,152].…”