Repurposing naproxen as a potential antiviral agent against SARS-CoV-2 (preprint)

ABSTRACT

The Outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in late 2019 in China and many other countries around the world necessitate immediate action to develop new drugs against the virus. Repurposing of existing drugs for new targets is a fast, safe and unexpansive approach for this goal. Studies have shown that naproxen could specifically interact with the RNA binding domain of nueclporteins of RNA viruses such as the influenza virus. Therefore, this study aimed to evaluate the binding properties of naproxen to the nucleocapsid protein of SARS-CoV-2. 3D structure of N and C terminal domains of SARS-CoV- 2 nucleocapsid were constructed and each were docked with naproxen and analyzed during 100 ns of molecular dynamics. The results showed that naproxen interacts with the N terminal domain of the nucleocapsid via two salt bridges with Arg 88 and 92 and a network of h-bonds. Molecular dynamics analysis was also revealed that all the coordinations of naproxen with N terminal domain were kept during 100 ns of simulation time. The results of this study provide insights how naproxen can specifically interact with the conserved RNA binding module of the nucleocapsid of SARS-CoV-2 that would inhibit the packaging of viral genome into capsid and virus assembly. Therefore we recommend evaluating the antiviral effects of naproxen against SARS-CoV-2 in in vitro studies and clinical trials.