Challenges of broad-spectrum antiviral drug discovery and development for emerging pathogens

Holli-Joi Martin; Jon-Michael Beasley; Enes Kelestemur; Zoe Sessions; Stephan Ludwig; Nathaniel J Moorman; Ralph Baric; Eugene N Muratov; Alexander Tropsha

doi:10.1016/j.drudis.2025.104486

Challenges of broad-spectrum antiviral drug discovery and development for emerging pathogens

Drug Discov Today. 2025 Sep 24;30(11):104486. doi: 10.1016/j.drudis.2025.104486. Online ahead of print.

Authors

Holli-Joi Martin¹, Jon-Michael Beasley¹, Enes Kelestemur¹, Zoe Sessions², Stephan Ludwig³, Nathaniel J Moorman⁴, Ralph Baric⁵, Eugene N Muratov⁶, Alexander Tropsha⁷

Affiliations

¹ Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
² Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19146, USA.
³ Institute of Virology Muenster (IVM), Westfaelische Wilhelms-University of Münster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
⁴ Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵ Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
⁶ Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: murik@email.unc.edu.
⁷ Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: alex_tropsha@unc.edu.

PMID: 41005563
DOI: 10.1016/j.drudis.2025.104486

Abstract

Broad-spectrum antiviral agent (BSAA) drugs are essential in the fight against viral, especially emerging, diseases. However, their development faces several challenges including insufficiently focused funding, fragmented research efforts and limited systematic data on BSAAs. In this review, we highlight these challenges, summarize accessible collections of data on antiviral compounds and viral targets, and explore possible directions toward the development of BSAAs. Whereas most existing BSAAs have been discovered serendipitously, we posit that rational, and feasible, design of direct-acting BSAAs should be focused on homologous targets found in viruses within a single viral family.

Keywords: antiviral research; broad spectrum antivirals; discovery pipeline; drug discovery; viral targets.

Publication types

Review