An Insilico Investigation: Repurposing FDA Approved Drugs Targeting Monkeypox Virus

Monkeypox viral infection is emerging as a significant threat and concern worldwide for the human population. Still, the available treatment options don’t meet the requirement, increasing the mortality and morbidity. This fosters the researchers to engage in the development of novel treatment strategies or drug repurposing to overcome the hurdle. With this background, the identification of potential drug targets can significantly amplify the development of potent drug molecules for the treatment. The proteins responsible for viral replication should be targeted, and hindering these proteins should be the key findings to reduce the morbidity and mortality. The literature review provides insight into two viral proteins, viral core Thymidylate Kinase (2V54) and DNA polymerase holoenzyme (8HG1), which are primarily responsible for disease aggravation. Sixty-four antiviral agents approved by the FDA were selected and evaluated against both viral proteins via simulation screening. These antiviral agents possess the capability to obstruct bacterial protein production, rendering them significant candidates for medication repurposing. According to the screening outcomes against DNA polymerase holoenzyme, the two leading compounds, Dolutegravir and Raltegravir, with docking values of – 10.0 and –9.7 kcal/mol, respectively, were chosen for further examination. Raltegravir and Etavirine, exhibiting docking scores of −10.0 and −9.6 kcal/mol, respectively, against thymidine kinase are the leading compounds identified following the validation of the protease with the pharmacological library. While investigating medications targeting proteinase, the top two molecules, Dolutegravir and Raltegravir, had the highest docking scores. These two medicinal compounds have significant inhibitory capabilities against MPXV proteinase Thymidine kinase and DNA polymerase protein. Ultimately, the current research illustrates the repurposing of antiviral medicines as a treatment for monkeypox viral infection.