An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

Abstract

AbstractMonkeypox is a zoonotic disease caused by the Poxviridiea family virus Monkeypox. According to the Centers for Disease Control and Prevention, 70,420 monkeypox virus infections had been reported in 107 countries as of October 6, 2022. New studies have concluded that the monkeypox outbreak is caused by a strain with a unique mutation, increasing the possibility that the virus may develop resistance to current medicines by accumulating mutations in therapeutic targets. As peptide‐based therapeutics impede the drug target through multiple interactions, it may offer a better therapeutic solution to the possible drug resistance issue related to monkeypox treatment. Therefore, in this work, we screened an antiviral peptide library, the CPP site 2.0 database, against the p37 target protein using molecular docking approaches. The p37 is required for the viral pathogen's successful egression and spread. The allergenicity and physicochemical properties of the peptides were thoroughly analyzed before the molecular docking studies for selecting druggable candidates. The interactions of the peptides bearing the highest docking score were validated further by using molecular dynamics (MD) simulation studies. Our investigation revealed that two cell‐penetrating peptides of the CPP site 2.0 database might effectively prevent the egression and spread of the MPXV by inhibiting p37. Following more testing, these peptides can be explored in developing peptide‐based therapies against the MPX therapy.