We last discussed Antiviral Research in May 2024 This is the 2025 Update.
Antiviral therapeutics entered a transformative phase in 2024-2025, marked by AI achieving 100% hit rates in drug discovery, twice-yearly injectable HIV prevention reaching near-perfect efficacy, and CRISPR therapies safely targeting viral DNA in humans for the first time. The $65 billion global market is evolving from treating individual viruses to developing broad-spectrum platforms that could address the next pandemic before it starts.
HIV: Long-Acting Revolution and Cure Progress
The FDA approval of lenacapavir (Yeztugo) for HIV prevention in June 2025 represents the most significant advancement since antiretroviral therapy was introduced. This Gilead capsid inhibitor requires just two subcutaneous injections per year and demonstrated 100% efficacy in the PURPOSE 1 trial (zero infections among 2,134 women) and 99.9% efficacy in PURPOSE 2. Science Magazine named it 2024's Breakthrough of the Year. Generic agreements will make it available for $40 per person annually in up to 120 countries starting in 2027, potentially transforming HIV prevention in resource-limited settings. Phase 1 data for once-yearly formulations showed maintained drug levels at 12 months.
HIV cure research transitioned from theory to reality with three new documented remission cases bringing the total to nine. The "Second Berlin Patient" maintained remission for 5+ years with only a single CCR5-delta32 mutation—not the double mutation previously thought necessary. The IMPAACT P1115 study showed that four of six infants starting ART within 48 hours of birth remained HIV-free for over one year after treatment pause, demonstrating ultra-early treatment can prevent reservoir establishment. Gilead's landmark South Africa cure trial achieved 30% of participants remaining off ART through week 48, with 20% through week 60—the first HIV cure trial in sub-Saharan Africa.
AI Drug Discovery Achieves Unprecedented Success
Model Medicines' GALILEO platform achieved what was considered impossible: screening 52 trillion molecules to identify 12 novel antivirals with a 100% in vitro hit rate, compared to typical 1-10% success rates. Published in January 2025, the chemical structures showed minimal similarity to known antivirals, representing truly first-in-class molecules. This validates one-shot generative AI's potential to compress drug discovery timelines from years to weeks.
Xaira Therapeutics raised $1 billion in April 2024—the largest biotech Series A ever—signaling mainstream investor confidence in AI drug discovery. The FDA published draft guidance in January 2025 for AI use in drug development, providing regulatory clarity. Over 500 FDA submissions with AI components occurred between 2016-2023.
Respiratory Viruses: First RSV Antiviral and COVID Evolution
RSV achieved its first antiviral with positive Phase 3 results. Shanghai Ark's ziresovir demonstrated 54.5% greater clinical score improvement versus placebo in hospitalized infants, with striking long-term benefits: 24-month follow-up showed 3.6 times lower recurrent wheezing rates—the first evidence that early antiviral intervention might prevent chronic respiratory disease. The WHO included ziresovir on its priority list in July 2025.
Enanta's EDP-323 demonstrated 85-87% reduction in RSV viral load and 97-98% reduction in infectious virus in Phase 2a challenge studies, with FDA Fast Track designation granted. For COVID-19, Shionogi's ensitrelvir achieved FDA NDA acceptance in September 2025 for post-exposure prophylaxis, with a PDUFA date of June 2026—potentially the first oral therapy for COVID prevention. Baloxavir marboxil demonstrated 32% reduction in influenza household transmission in the CENTERSTONE Phase 3 trial published in NEJM April 2025, representing the first Phase 3 demonstration of antiviral transmission reduction.
CRISPR Validation and Broad-Spectrum Breakthroughs
Excision BioTherapeutics' EBT-101 represents a watershed: the first CRISPR antiviral therapy to generate human clinical data. The Phase 1/2 HIV trial demonstrated excellent safety—no serious adverse events or dose-limiting toxicities—establishing proof-of-concept that CRISPR can target viral DNA in humans. While most participants rebounded after stopping ART, one maintained suppression for 16 weeks, significantly longer than typical 2-4 week rebound times.
Synthetic carbohydrate receptors achieved the most dramatic broad-spectrum results to date. CUNY and UCLA researchers published in Science Advances August 2025 that nanoparticles displaying carbohydrate-binding molecules achieved 90% survival rates in COVID-19 mouse models after a single dose with zero toxicity. Four designs showed activity across all six tested deadly viruses: SARS-CoV-1, SARS-CoV-2, MERS-CoV, Nipah, Hendra, and Ebola. The virucidal mechanism irreversibly inactivates viral particles by binding conserved glycans on viral surfaces.
Market Dynamics and Strategic Opportunities
The global antiviral market reached $60-65 billion in 2024, projected to grow to $69-85 billion by 2030-2035 at 3.6-6.2% CAGR. Critically, no novel antiviral drugs received FDA approval among the 50 novel drugs approved in 2024, indicating the field remains in development mode. Geographic growth is fastest in Asia-Pacific at 6.12% CAGR, with China the most lucrative market.
Biotech funding recovered with $26 billion raised in 2024 versus $23.3 billion in 2023, though consolidating toward larger "mega rounds." Antiviral-specific investment remains limited outside pandemic preparedness, with obesity drugs seeing 550% increases. However, platform technologies command premium valuations: Xaira's $1 billion raise demonstrates that technologies with multiple shots on goal far exceed single-asset valuations.
The WHO pandemic agreement adopted May 2025 established frameworks for equitable therapeutic access. NIH's Antiviral Program for Pandemics targets five high-risk viral families, though proposed NIH budget cuts of 40% threaten momentum. The 100 Days Mission seeks to compress pathogen-to-countermeasure timelines to just over three months—impossible without platform technologies.
Future Outlook
The convergence of AI maturation, CRISPR validation, long-acting formulation success, and global policy alignment creates conditions for transformation. For innovators and investors, the opportunity lies in platform technologies addressing entire viral families rather than incremental improvements to existing drugs. Technologies demonstrating clinical proof-of-concept with broad applicability represent exceptional risk-adjusted opportunities—the difference between building a better mousetrap and inventing CRISPR for viral genomes.
Key Sources
WHO - Lenacapavir for HIV Prevention
https://www.who.int/news/item/14-07-2025-who-recommends-injectable-lenacapavir-for-hiv-prevention
FDA - Gilead Lenacapavir Approval
https://www.gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection
New England Journal of Medicine - Baloxavir Transmission Study
https://www.nejm.org/doi/full/10.1056/NEJMoa2413156
New England Journal of Medicine - Hepatitis D Bulevirtide Trial
https://www.nejm.org/doi/full/10.1056/NEJMoa2213429
NIH - Antiviral Program for Pandemics
https://www.niaid.nih.gov/research/antivirals
Shionogi - Ensitrelvir for COVID-19 Prevention
https://www.shionogi.com/global/en/news/2025/09/20250903.html
University of New Mexico - First HPV Antiviral Treatment
https://hsc.unm.edu/news/2025/02/unmccc-first-hpv-antiviral-treatment-ozbun.html
ArkBio - Ziresovir RSV Antiviral Phase 3 Results
https://www.arkbiosciences.com/80/100
CRISPR Medicine News - EBT-101 HIV Gene Therapy
https://crisprmedicinenews.com/news/clinical-trial-update-positive-clinical-data-for-first-ever-crispr-therapy-for-hiv/
Fred Hutchinson Cancer Center - Herpes Gene Editing
https://www.fredhutch.org/en/news/releases/2024/05/herpes-cure-with-gene-editing-makes-progress-in-laboratory-studi.html
Model Medicines - AI Drug Discovery Platform
https://modelmedicines.com/newsroom/the-future-of-drug-discovery-2025-as-the-inflection-year-for-hybrid-ai-and-quantum-computing
