How Remdesivir and Molnupiravir Interact with MERS-CoV

Overview

With the worldwide attention that coronavirus disease 2019 (COVID-19) has received over the past year, renewed attention has been focused on the related illness, Middle East Respiratory Syndrome (MERS). The causal infectious agent for MERS is also a coronavirus (MERS-CoV). In previous studies, the antiviral medications remdesivir and molnupiravir have been shown to have therapeutic benefits for patients infected with MERS-CoV. This study sought to better understand how remdesivir and molnupiravir interact with the MER-CoV RNA-dependent RNA polymerase, and where the antiviral medications most likely bind within the nsp7, nsp8, and nsp12 protein complex that composes the RNA-dependent RNA polymerase. The interactions between molnupiravir and remdesivir and another coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), were modeled to give more information about the behavior of the antiviral medications across the complete Coronaviridae family. AutoDock Vina was used to model the interaction between the protein complex and each of the antiviral drugs. Both molnupiravir and remdesivir docked in nearly the same location for both MERS-CoV and SARS-CoV, suggesting that molnupiravir and remdesivir could have a similar effect on the two viruses. Both of the antiviral medications docked to the nsp12 protein in MERS-CoV and SARS-CoV, suggesting that the nsp12 protein is particularly susceptible to binding by antiviral agents, and that when the drugs are bound to the protein, the effectiveness of the polymerase is inhibited. The results from this study could lead to the development of new antiviral medications that can better target the identified site of binding within the RNA-dependent RNA polymerase of both MERS-CoV and similarly structured coronaviruses.