Inspection on the Mechanism of SARS-CoV-2 Inhibition by Penciclovir: A Molecular Dynamic Study

In recent years, humanity has had to face a critical pandemic due to SARS-CoV-2. In the rapid search for effective drugs against this RNA-positive virus, the repurposing of already existing nucleotide/nucleoside analogs able to stop RNA replication by inhibiting the RNA-dependent RNA polymerase enzyme has been evaluated. In this process, a valid contribution has been the use of in silico experiments, which allow for a rapid evaluation of the possible effectiveness of the proposed drugs. Here we propose a molecular dynamic study to provide insight into the inhibition mechanism of Penciclovir, a nucleotide analog on the RNA-dependent RNA polymerase enzyme. Besides the presented results, in this article, for the first time, molecular dynamic simulations have been performed considering not only the RNA-dependent RNA polymerase protein, but also its cofactors (fundamental for RNA replication) and double-strand RNA.

Automated summary

In the search for effective drugs against SARS-CoV-2, existing nucleotide/nucleoside analogs have been repurposed to inhibit RNA replication through the inhibition of the RNA-dependent RNA polymerase enzyme. In silico experiments have been used to rapidly evaluate the potential effectiveness of these drugs. This study employs molecular dynamic simulations to analyze the inhibition mechanism of Penciclovir, a nucleotide analog, on the RNA-dependent RNA polymerase enzyme.