Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach.
Md Abdullah Al Mashud, Ajoy Kumer, Nobendu Mukerjee, Akhel Chandro, Swastika Maitra, Unesco Chakma, Abhijit Dey, Shopnil Akash, Athanasiosis Alexiou, Azmat Ali Khan, Amer M Alanazi, Arabinda Ghosh, Kow-Tong Chen, Rohit Sharma
Author Information
Md Abdullah Al Mashud: Biophysics and Biomedicine Research Lab, Department of Electrical & Electronic Engineering, Islamic University, Kushtia, Bangladesh.
Ajoy Kumer: Laboratory of Computational Research for Drug Design and Material Science, Department of Chemistry, European University of Bangladesh, Dhaka, Bangladesh.
Nobendu Mukerjee: Department of Microbiology, West Bengal State University, West Bengal, Kolkata, India.
Akhel Chandro: Department of Poultry Science, Faculty of Animal Science & Veterinary Medicine, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh.
Swastika Maitra: Department of Microbiology, Adamas University, West Bengal, Kolkata, India.
Unesco Chakma: Laboratory of Computational Research for Drug Design and Material Science, Department of Chemistry, European University of Bangladesh, Dhaka, Bangladesh.
Abhijit Dey: Department of Life Sciences, Presidency University, Kolkata, West Bengal, India.
Shopnil Akash: Department of Pharmacy, Daffodil International University, Sukrabad, Dhaka, Bangladesh.
Athanasiosis Alexiou: Department of Science and Engineering, Novel Global Community Educational Foundation, Habersham, NSW, Australia.
Azmat Ali Khan: Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Amer M Alanazi: Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Arabinda Ghosh: Microbiology Division, Department of Botany, Gauhati University, Assam, India.
Kow-Tong Chen: Department of Occupational Medicine, Tainan Municipal Hospital (managed by Show Chwan Medical Care Corporation), Tainan, Taiwan.
Rohit Sharma: Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study's primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses.
