AI-driven drug repurposing and binding pose meta dynamics identifies novel targets for monkeypox virus. Issue 5 (May 2023)

• Record Type: Journal Article
• Authors: Patel, Chirag N.; Mall, Raghvendra; Bensmail, Halima
• Is Part Of: Journal of infection and public health. Volume 16:Issue 5(2023)
• Page Start: 799
• Page End: 807
• Publication Date: 2023-05
• Subjects: Monkeypox virus -- Double-stranded DNA -- DeepRepurpose -- Deep learning -- Molecular docking and binding pose metadynamics; Communicable diseases -- Periodicals; Public health -- Periodicals; Epidemiology -- Periodicals; Nosocomial infections -- Prevention -- Periodicals; Medical microbiology -- Periodicals; 614.4
• DOI: 10.1016/j.jiph.2023.03.007
• Languages: English
• ISSNs: 1876-0341

Abstract

Abstract: Monkeypox virus (MPXV) was confirmed in May 2022 and designated a global health emergency by WHO in July 2022. MPX virions are big, enclosed, brick-shaped, and contain a linear, double-stranded DNA genome as well as enzymes. MPXV particles bind to the host cell membrane via a variety of viral-host protein interactions. As a result, the wrapped structure is a potential therapeutic target. DeepRepurpose, an artificial intelligence-based compound-viral proteins interaction framework, was used via a transfer learning setting to prioritize a set of FDA approved and investigational drugs which can potentially inhibit MPXV viral proteins. To filter and narrow down the lead compounds from curated collections of pharmaceutical compounds, we used a rigorous computational framework that included homology modeling, molecular docking, dynamic simulations, binding free energy calculations, and binding pose metadynamics. We identified Elvitegravir as a potential inhibitor of MPXV virus using our comprehensive pipeline.