Screening of potential inhibitors against structural proteins from Monkeypox and related viruses of Poxviridae family via docking and molecular dynamics simulation

Monkeypox virus (MPXV) is an orthopoxvirus which causes zoonotic infection in humans. Even though sporadic cases of this infection are limited to the African continent, but if the infection continues to increase unabated, it can be a cause of serious concern for the human populace. Smallpox vaccination has been in use against monkeypox infection but it only provides mild protection. In the current study, we have screened novel small molecules (estrone fused heterocycles (EH1-EH7)) exhibiting good binding with monkeypox virus protein and related proteins from Poxviridae family of viruses via computational approaches. EH1-7 series of small molecules selected for the work have been synthesized via cycloaddition methodology. Docking and Molecular Dynamics (MD) results highlight EH4 compound to have strong binding affinity towards monkeypox and other related viral proteins selected for the study. Thus, computational outcomes suggest EH4 as a good candidate against monkeypox. Currently, no antiviral medication has been approved against monkeypox and the treatment is only via therapeutics available for smallpox and related conditions that may be helpful against monkeypox. Our study is thus an attempt to screen novel compounds against monkeypox infection, which would, in turn, facilitate development of novel therapeutics against Poxviridae family.HIGHLIGHTS center dot Monkeypox infection is a public health emergency and necessitates immediate drug discovery.center dot Molecular docking study to screen estrone-fused heterocycles compounds against Monkeypox and other orthopoxviruses.center dot Molecular dynamics simulations revealed interaction/high binding affinities among EH4 heterocyclic compound and profilin-like protein from the monkeypox virus.center dot Estrone-fused heterocycles compounds are promising anti-viral agents as per our in silico analysis.center dot Our study provides evidence for investigating estrone-fused heterocycles compounds for further pharmacological interventions.