Abstract
Monkeypox, a viral zoonotic disease caused by the monkeypox virus (MPXV), has recently become a significant global health threat due to increased human-to-human transmission. As of November 2023, the Mpox outbreak had impacted 116 countries worldwide, with a total of 92,783 confirmed cases and 171 reported deaths. With limited antiviral options available, natural plant-based compounds like Andrographis paniculata have shown promise for their antimicrobial and antiviral properties. This study explores the potential of bioactive compounds from A. paniculata against monkeypox viral targets through computational methods. Protein structures 4E90, 8B07, 8C9K, 8IZT and 8J8G were obtained from the Protein Data Bank (PDB), and molecular dynamic simulation studies were conducted using the Schrödinger Suite. Furthermore, the trajectory analysis assessed the stability and binding affinity of the ligand-protein complexes. The compounds andrographolide, luteolin, and andrographidin-A demonstrated strong binding interactions and stable protein-ligand complexes, along with favorable thermodynamic profiles, supporting their potential as promising therapeutic candidates for monkeypox treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00423-4.