High-Throughput Insilico Drug Screen against Mpox Targeted Proteins in Comparison with Repurposed Antiviral Drugs against Natural Compounds
Hemanth Kumar Manikyam
*
Department of Chemistry, Faculty of Science, North East Frontier Technical University- Aalo Post Office, West Siang Distt, National Highway 229, Aalo, Arunachal Pradesh 791001, India.
Sandeep Balvant Patil
Dr Shivajirao Kadam College of Pharmacy Kasbe digaraj, Sangli, Maharashtra, India.
Nazim Hussain
Department of Pharmaceutical Sciences - North East Frontier Technical University- Aalo Post Office, West Siang Distt, National Highway 229, Aalo, Arunachal Pradesh 791001, India.
R. Edison Eegai Vallal
Department of Biotechnology, Adhiyamaan college of Engineering, Hosur, Tamilnadu 635109, India.
Shikha Sharma
HIPAA Compliance officer Lab testing API-USA and Faculty at Punjab University- Chandigarh, India.
Abhinandan Ravsaheb Patil
D Y Patil College of Pharmacy, Kolhapur, India.
*Author to whom correspondence should be addressed.
Abstract
The recent resurgence of the Monkeypox Virus (MPXV) has prompted increased efforts to discover effective antiviral treatments. This study utilized an in silico docking approach with CB Dock2 to assess both natural compounds and repurposed antiviral medications. We concentrated on several critical viral targets for inhibition, specifically VP39 2'-O Methyltransferase, viral topoisomerase-DNA complexes, and poxin. Our results identified a number of natural substances, including Physalin A, Sitoindoside IX, Withanolide, Shatavarin 1, Kutkoside, and Berberine HCl, as promising inhibitors. Tecovirimat was found to be the most effective among the repurposed antivirals. Notably, natural products like Withanolide, Sitoindoside IX, and Physalin A showed significant inhibitory potential based on their Vina scores and binding affinities, suggesting they may serve as alternative therapeutic options. Tecovirimat consistently proved to be the most powerful inhibitor among repurposed antivirals across all examined targets, reinforcing its importance in combating MPXV.
Keywords: Monkeypox Virus (MPXV), VP39 2'-O methyltransferase, viral topoisomerase-DNA complexes, poxin, Physalin A, sitoindoside IX, withanolide, shatavarin 1, kutkoside and berberine hydrochloride, tecovirimat, In silico high-throughput, drug targets, protein Data Bank ID-8B07, Protein Data Bank ID-3IGC, Protein Data Bank ID-8C9K