Screening of potential inhibitors against structural proteins from Monkeypox and related viruses of <i>Poxviridae</i> family via docking and molecular dynamics simulation
Creators: name: Kaur, Mandeep
name: Sharma, Akanksha
name: Kaur, Harjeet
name: Singh, Manjari
name: Devi, Bharti
name: Raj, A. R. Naresh
name: Sood, Vikas
name: Pandey, Ankur
name: Gartia, Janeka
name: Kumar, Rajnish
name: Babu, Adukamparai R. Suresh
name: Singh, Gurpal
name: Barnwal, Ravi Pratap
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology
subject: Computational Biology

description: 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 <i>Poxviridae</i> family of viruses <i>via</i> computational approaches. EH1-7 series of small molecules selected for the work have been synthesized <i>via</i> 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 <i>via</i> 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 <i>Poxviridae</i> family. 
HIGHLIGHTSMonkeypox infection is a public health emergency and necessitates immediate drug discovery.Molecular docking study to screen estrone-fused heterocycles compounds against Monkeypox and other orthopoxviruses.Molecular dynamics simulations revealed interaction/high binding affinities among EH4 heterocyclic compound and profilin-like protein from the monkeypox virus.Estrone-fused heterocycles compounds are promising anti-viral agents as per our <i>in silico</i> analysis.Our study provides evidence for investigating estrone-fused heterocycles compounds for further pharmacological interventions. Monkeypox infection is a public health emergency and necessitates immediate drug discovery. Molecular docking study to screen estrone-fused heterocycles compounds against Monkeypox and other orthopoxviruses. Molecular dynamics simulations revealed interaction/high binding affinities among EH4 heterocyclic compound and profilin-like protein from the monkeypox virus. Estrone-fused heterocycles compounds are promising anti-viral agents as per our <i>in silico</i> analysis. Our study provides evidence for investigating estrone-fused heterocycles compounds for further pharmacological interventions. Communicated by Ramaswamy H. Sarma <b>Monkeypox:</b> This orthopoxvirus leads to mpox (monkeypox) disease which shows symptoms similar to that smallpox, however to less severe extent. <b>Poxviridae family:</b> This is commonly a family of double-stranded DNA viruses. The natural hosts for these viruses are arthropods and Vertebrates. <b>Molecular Dynamic simulation:</b> MD simulation is crucial for determining the ligand’s stability and revealing the duration of its interaction with the respective macromolecular structure. <b>Molecular Docking:</b> Molecular docking aids in determining specific sites where the ligand binds with the macromolecule as well as its binding affinity. Bioinformatics tools such as docking have been widely employed for aiding drug discovery efforts. <b>Protein binding energy:</b> On docking protein with the ligand, the binding energy shows the free energy change during binding process between protein-ligand.