Why Small Molecules Matter
Fast, Flexible, and Accessible Therapy for All
What Are Small-Molecule Antivirals?
Small-molecule drugs are low molecular weight compounds, typically administered orally in
tablet or capsule form. In antiviral therapy, they work by inhibiting viral enzymes or proteins essential for replication (e.g., polymerases, proteases), or by targeting host cell factors required for the viral life cycle. Unlike biologics such as monoclonal antibodies or mRNA vaccines, small molecules are chemically synthesized and generally easier to produce and
distribute.
Speed of Development
In public health emergencies, time is critical. Small-molecule antivirals can be developed and
deployed much faster than vaccines or biologics. Two key strategies are used:
● Drug repurposing: Screening existing drugs for antiviral activity, which shortens
timeframes by leveraging pre-existing safety and pharmacokinetic data. For example,
remdesivir, initially developed for Ebola, was rapidly redeployed against SARS-CoV-2.
● De novo synthesis and high-throughput screening: Using modern chemistry and
robotics to evaluate thousands of compounds in vitro. AI-driven approaches further
accelerate this process by predicting the most promising candidates.
The COVID-19 pandemic demonstrated the potential of this approach: Paxlovid
(nirmatrelvir/ritonavir), a novel oral protease inhibitor, was developed and authorized in under
two years.
Manufacturing and Global Access
Small molecules are chemically stable, often requiring no refrigeration, and can be produced in large quantities using industrial-scale synthesis. This makes them particularly suited for global deployment, especially in resource-limited settings. Oral antivirals like Paxlovid can be distributed via pharmacies, taken at home, and administered without clinical supervision, improving patient adherence and reducing strain on hospitals.
Cost and Equity
Once approved, the cost per dose of small-molecule drugs is typically lower than that of
biologics. Their affordability and ease of distribution make them a cornerstone for equitable access during pandemics. This is particularly important when dealing with high caseloads, where scalable and accessible solutions are needed to reach vulnerable populations.
AVITHRAPID and the Road Ahead
The AVITHRAPID consortium aims to build a pipeline of small-molecule antivirals that target both viral and host factors across a range of priority pathogens. Using a combination of medicinal chemistry, structural biology, AI, and in vivo validation, the project aims to fast-track promising candidates into clinical development. By investing in small molecules today, we prepare for the health emergencies of tomorrow with tools that are fast, flexible, and available to all.