AI-driven discovery of antiretroviral drug bictegravir and etravirine as inhibitors against monkeypox and related poxviruses
Year: 2025
Type: article
Abstract: Monkeypox virus (MPXV) caused the 2022-2023 global mpox and the concurrent outbreaks in Africa, disproportionately affecting immunocompromised individuals such as people living with HIV. With no approved treatment available, we developed a robust artificial intelligence (AI) pipeline for discovering broad-spectrum poxvirus inhibitors that target the viral DNA polymerases. Among the identified leading candidates, we found that the clinically used antiretroviral drugs bictegravir and etravirine potently inhibit MPXV clade Ia, Ib and IIb infections in human intestinal and skin organoids. The broad anti-poxvirus activities of bictegravir and etravirine were further demonstrated against infections of other Orthopoxviruses such as vaccinia virus and cowpox virus. These findings support the repurposing of bictegravir and etravirine for treating mpox, especially for patients co-infected with HIV, warranting follow-up clinical investigation. The established AI pipeline and our antiviral drug discovery strategies bear major implications for responding to the ongoing mpox emergency and preparing for future poxvirus epidemics.
Source: Communications Biology
Institutions: Shenyang Pharmaceutical University, Erasmus MC, Hacettepe University, Leiden University Medical Center, Novo Nordisk Foundation Center for Stem Cell Medicine, University of Minnesota, University of Cape Coast, Institute of Human Virology, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Laboratoire Biologie à Grande Échelle, Gazi University, Xuzhou Medical College
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W4416910002