Chain-Engineering-Based De Novo Drug Design against MPXVgp169 Virulent Protein of Monkeypox Virus: A Molecular Modification Approach

Abstract

The unexpected appearance of the monkeypox virus and the extensive geographic dispersal of cases have prompted researchers to concentrate on potential therapeutic approaches. In addition to its vaccine build techniques, there should be some multiple integrated antiviral active compounds because of the MPV (monkeypox virus) outbreak in 2022. This study offers a computational engineering-based de novo drug discovery mediated by random antiviral active compounds that were screened against the virulent protein MPXVgp169, as one of the key players directing the pathogenesis of the virus. The screening of these candidates was supported by the use of 72 antiviral active compounds. The top candidate with the lowest binding affinity was selected for the engineering of chains or atoms. Literature assisted to identify toxic chains or atoms that were impeding the stability and effectiveness of antiviral compounds to modify them for enhanced efficacy. With a binding affinity of −9.4 Kcal/mol after chain, the lipophilicity of 0.41, the water solubility of 2.51 as soluble, and synthetic accessibility of 6.6, chain-engineered dolutegravir was one of the best active compounds, as proved by the computational engineering analysis. This study will revolutionize the era of drug engineering as a potential therapeutic strategy for monkeypox infection.