Zafer Saad Al Shehri, Faez Falah Alshehri and Abdur Rehman* Pages 1 - 21 ( 21 )
Introduction: The emergence of the monkeypox virus (MPXV) as a zoonotic threat has necessitated the development of effective treatments, particularly after it spread to regions outside of Central and Western Africa, such as the 2003 outbreak in the United States. Our groundbreaking study identifies CDK1 and TOP2A as key proteins in the pathogenesis of MPXV infection, utilizing network pharmacology to target these proteins for the first time. CDK1 and TOP2A, previously known for their roles in cell reprogramming, emerge as critical targets in our strategy to combat the virus.
Methods: By targeting CDK1 and TOP2A, proteins integral to cell reprogramming, with small molecules identified in our study, such as carnosic acid, rosmarinic acid, and coclaurine, we propose a novel method not only to inhibit the replication of the monkeypox virus but also to harness cellular plasticity for therapeutic purposes. The identification and targeting of these proteins with specific compounds disrupt the virus's life cycle and simultaneously enhance the efficiency of cell reprogramming.
Results: This dual-action approach leverages the inherent plasticity of cellular reprogramming processes to combat the virus, showcasing a pioneering step in the use of regenerative medicine principles for antiviral strategies. Moreover, molecular docking and dynamic simulations strengthen our findings by demonstrating a strong binding affinity between TOP2A and CDK1, validating the synergistic effects of our identified small molecules.
Conclusion: Our research thus opens new avenues for addressing viral threats like monkeypox, utilizing the convergence of virology, network pharmacology, and cellular reprogramming to pave the way for innovative treatments.
Monkeypox virus, network pharmacology, ligand interaction, molecular docking, dynamic simulations, bioinformatics analysis.