The Indispensable Value of Small-Molecule Antivirals in Epidemic and Pandemic Preparedness.

Draghia-Akli, Ruxandra; Hill, Nina M; Altevogt, Bruce; Bradley, Kenneth; Chibale, Kelly; Cihlar, Tomas; Clinch, Barry; Demarest, James F et al. · Clin Infect Dis · 2026

review · Level V

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Abstract

Harbingers of infectious viral pandemics, such as the H1N1 influenza, SARS, Zika, Ebola, MERS, and SARS-CoV-2, caused major outbreaks in the first two  decades of the 21st century. Despite warnings, therapeutic tools that could be rapidly and sustainably scaled at a global level when SARS-CoV-2 emerged were lacking. Small-molecule antivirals can play a crucial role in both individual patient care and broader public health strategies for controlling and mitigating the impact of viral diseases. Despite their utility, the lack of R&D investment in this class of intervention has prevented the world from reaping the benefits they can deliver. The INTREPID Alliance 2025 publication of the Antiviral Clinical and Preclinical Development Landscape-4th Edition, revealed significant gaps in the development pipeline. No antivirals are in clinical development for 4 of the 13 viral families designated by the World Health Organization as viral families of pandemic and endemic concern.

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