Computational evidence on repurposing the anti-influenza drugs baloxavir acid and baloxavir marboxil against COVID-19

TL;DR

This study uses molecular docking to evaluate the potential of influenza drugs baloxavir acid and baloxavir marboxil as repurposed therapeutics against COVID-19 by targeting key viral proteins.

Contribution

It provides computational evidence that baloxavir acid may be more effective than baloxavir marboxil in inhibiting SARS-CoV-2 proteins, supporting drug repurposing efforts.

Findings

Baloxavir acid binds effectively to SARS-CoV-2 main protease and RdRp.

Baloxavir marboxil binds only to RdRp.

Baloxavir acid shows stronger binding affinity to RdRp than baloxavir marboxil.

Abstract

The main reasons for the ongoing COVID-19 (coronavirus disease 2019) pandemic are the unavailability of recommended efficacious drugs or vaccines along with the human to human transmission nature of SARS-CoV-2 virus. So, there is urgent need to search appropriate therapeutic approach by repurposing approved drugs. In this communication, molecular docking analyses of two influenza antiviral drugs baloxavir acid (BXA) and baloxavir marboxil (BXM) were performed with the three therapeutic target proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp). The molecular docking results of both the drugs BXA and BXM were analysed and compared. The investigational drug BXA binds at the active site of Mpro and RdRp, whereas the approved drug BXM binds only at the active site of RdRp. Also, comparison of dock score revealed that BXA is binding more effectively at the active site of RdRp than BXM. The computational molecular docking revealed that the drug BXA may be more effective against COVID-19 as compared to BXM.