We last discussed Antiviral Research in May 2024 This is the 2025 Update.
In a nondescript lab at Model Medicines this year, an artificial intelligence system did something that would have been dismissed as impossible just five years ago. The company's GALILEO platform screened 52 trillion molecules—more than there are stars in the Milky Way—and identified 12 entirely new antiviral compounds. Every single one worked in lab tests. That's a 100% success rate in a field where hitting 10% is considered exceptional.
It's one data point in what's shaping up to be the most transformative period in antiviral medicine since the discovery of antibiotics. Across the world, scientists are reporting breakthroughs that read like science fiction: twice-yearly HIV prevention injections showing 100% efficacy in trials of thousands of women in sub-Saharan Africa. CRISPR gene-editing therapies safely cutting viral DNA out of human cells for the first time. An RSV drug that not only treats infant infections but appears to prevent chronic lung disease years later.
"This is genuinely unprecedented," says one researcher involved in HIV cure trials who spoke on background. "We're seeing multiple approaches that were theoretical five years ago producing actual clinical results today."
The timing matters. COVID-19 exposed critical weaknesses in how we respond to viral threats, prompting a massive reorientation toward pandemic preparedness. The WHO adopted its pandemic agreement in May 2025. NIH launched a dedicated Antiviral Program targeting the five viral families most likely to cause the next outbreak. And crucially, technologies that seemed perpetually "ten years away"—particularly AI drug discovery and gene therapy—are suddenly delivering on decades of promise.
This isn't incremental progress. The field is shifting from treating individual viruses to developing platforms that work across entire viral families, from managing chronic disease to attempting functional cures, and from reactive development to proactive preparation. For the first time, we're building tools to address pandemics before they start.
The HIV prevention breakthrough that changes everything
On June 18, 2025, the FDA approved something remarkable: a drug you take twice per year that provides complete protection against HIV.
Lenacapavir, sold as Yeztugo by Gilead Sciences, demonstrated results in clinical trials that even its developers found startling. In the PURPOSE 1 study, which enrolled 2,134 cisgender women in South Africa and Uganda—populations with some of the world's highest HIV rates—not a single participant who received the drug contracted HIV. Zero infections. In the PURPOSE 2 trial of 2,179 participants across seven countries, only two infections occurred. Science Magazine named it the 2024 Breakthrough of the Year.
"The 100% efficacy number is genuinely stunning," says Dr. Sharon Lewin, president-elect of the International AIDS Society, in published comments. "We don't usually see that in prevention trials."
The drug works by targeting the viral capsid—the protein shell protecting HIV's genetic material—and interfering with multiple steps in the virus's lifecycle simultaneously. That multi-pronged attack makes it extremely difficult for the virus to develop resistance through mutations.
What makes this particularly significant is the dosing schedule. Current HIV prevention requires daily pills, which sounds simple but creates adherence challenges that undermine effectiveness in real-world settings. Remembering to take a pill every single day when you're not sick is harder than it sounds, especially for young people or those in unstable life situations. Two injections per year changes the equation entirely.
The global implications are substantial. Gilead has committed to making generic versions available in up to 120 countries for approximately $40 per person annually—a fraction of what daily prevention costs in the developed world. The WHO recommended lenacapavir just weeks after FDA approval, and the drug received European authorization in September 2025.
Gilead isn't stopping there. At the Conference on Retroviruses and Opportunistic Infections in March 2025, researchers presented Phase 1 data on once-yearly formulations that maintain effective drug levels for 12 months. Phase 3 trials are planned for later this year. The company is also combining lenacapavir with broadly neutralizing antibodies to create potential twice-yearly complete treatment regimens—not just prevention, but full HIV therapy requiring only two visits per year.
Other long-acting approaches are advancing in parallel. ViiV Healthcare's Cabenuva, an every-two-month injection already approved for treatment, continues showing strong real-world effectiveness in studies of thousands of patients. Merck has multiple weekly oral regimens in late-stage development, with one combination expected to reach FDA decision by April 2026.
The race toward ultra-long-acting HIV medicines represents more than convenience. For the estimated 39.9 million people living with HIV globally and the millions more at risk, the difference between daily medication and twice-yearly treatment could mean the difference between the epidemic's continuation and its eventual end.
Functional cure research delivers unprecedented remissions
The holy grail of HIV research—completely eliminating the virus from the body—took meaningful steps forward in 2024-2025, with three new cases of long-term remission bringing the documented total to nine people who've stopped treatment and remain virus-free for years.
The most significant may be the "Second Berlin Patient," presented at the International AIDS Conference in July 2024. This 60-year-old German man received a stem cell transplant in 2015 using donor cells with only a single copy of the CCR5-delta32 mutation—a genetic variant that makes cells resistant to most HIV strains. Previous cure cases, starting with the famous "Berlin Patient" Timothy Ray Brown in 2007, used donors with two copies of the mutation, leading researchers to believe that double mutation was essential.
It apparently isn't. The Second Berlin Patient stopped antiretroviral therapy in late 2018 and has maintained complete HIV remission for over five years, with no detectable virus in ultrasensitive assays of blood, tissue biopsies, or any other body compartment tested. If a single copy of this mutation is sufficient, the pool of potential curative transplant donors expands dramatically.
Even more intriguing is the "Chicago Patient," who demonstrated something entirely new: sustained remission after viral rebound. This challenges the assumption that any detectable virus after stopping treatment means cure attempts have failed. The patient experienced rebound, restarted medications, then stopped again after two years and has now maintained remission for over 10 months—suggesting the immune system may have learned something during the first exposure that enabled control the second time.
Perhaps most hopeful are the pediatric cases. In a study of 54 infants who acquired HIV in utero but started treatment within 48 hours of birth, four of six who later stopped medication remained virus-free for over a year. Only two experienced quick rebound. The findings suggest that catching HIV at the absolute earliest moment—before the virus establishes its long-lived reservoir in resting immune cells—may make functional cure achievable without requiring transplants or complex therapies.
"These kids started treatment within two days of life," notes one pediatric HIV specialist familiar with the results. "That's a narrow window, but it shows the reservoir isn't inevitable if you act fast enough."
Antibody-based approaches are producing striking results without requiring transplants at all. In the RIO study, people treated during early HIV infection received two long-acting broadly neutralizing antibodies—engineered immune proteins that target parts of the virus that rarely mutate—then stopped their regular medications. At 48 weeks, 57% remained without viral rebound compared to just 5% of those who received placebo. Some participants have now maintained viral suppression for over a year without antiretroviral drugs.
A South African trial took this approach to the population most affected by HIV: cisgender women in sub-Saharan Africa. Twenty participants received a combination of immune-stimulating drugs and antibodies, then stopped treatment. Remarkably, 30% remained off medications through 48 weeks, and 20% made it through 60 weeks—the first demonstration that complex cure strategies can work in resource-limited settings.
"That trial happening in South Africa isn't just scientifically important," one AIDS researcher told me. "It's politically and ethically essential. You can't develop cure strategies only for wealthy countries when the epidemic is concentrated in Africa."
Gene editing moves from theory to human trials
On a more experimental front, CRISPR gene-editing technology transitioned from laboratory curiosity to validated human therapy in 2024-2025, with the first published results from people receiving gene-edited cells designed to attack HIV.
Excision BioTherapeutics' EBT-101 uses the CRISPR-Cas9 system—molecular scissors that can cut DNA at precise locations—delivered via modified viruses that don't replicate. The therapy carries two guide RNAs designed to target three sites on the integrated HIV genome in infected cells, with the goal of excising the viral DNA entirely and permanently.
The 48-week results from the Phase 1/2 trial, presented at the International AIDS Conference in 2024, showed something crucial: safety. No serious adverse events. No dose-limiting toxicities. The gene-editing machinery cleared from blood within six months. Given concerns about CRISPR potentially causing unintended cuts at off-target sites or triggering immune reactions, demonstrating safety in humans is foundational.
Efficacy proved more complicated. When participants stopped their antiretroviral medications, most experienced viral rebound—though one participant maintained suppression for 16 weeks, significantly longer than the typical 2-4 weeks. Some participants showed measurable reductions in their viral reservoir, though responses were variable.
The challenges are significant. HIV integrates randomly into the genome, sometimes landing in regions where gene-editing machinery can't easily reach. Some participants had viral strains that didn't perfectly match the guide RNA sequences, reducing cutting efficiency. And eliminating 99.9% of infected cells may not be enough—the virus can rebound from tiny remaining reservoirs.
But proving that CRISPR can safely target viral DNA in humans opens the door. Excision is developing next-generation products with improved targeting. The company also has programs for herpes simplex virus—potentially an easier target since HSV DNA doesn't integrate into chromosomes but remains in separate circles in nerve cells—and hepatitis B, which similarly maintains episomal DNA in liver cells.
The broader context favors gene editing. Casgevy, the first approved CRISPR therapy for sickle cell disease authorized in 2023, demonstrated the platform's safety in humans. Multiple CRISPR trials are advancing for cancer and genetic diseases, building regulatory familiarity. The question isn't whether gene editing is safe enough—it's whether targeting efficiency can reach the near-perfect levels needed to eliminate viruses that persist at extremely low but rebounding copy numbers.
Fred Hutchinson Cancer Center researchers reported in May 2024 that their simplified herpes gene-editing approach achieved 90% elimination in oral herpes models and 97% in genital herpes models, with substantial reductions in viral shedding. The team is preparing for clinical trials with regulatory guidance, funded by NIH and thousands of individual donors who want to see herpes research advance.
"The technology works," one gene therapy researcher told me. "Now it's about optimization—making it work well enough to matter clinically."
HPV remains stubborn, but progress edges forward
Human papillomavirus presents one of medicine's most frustrating puzzles. Unlike herpes or HIV, which encode their own enzymes that can be targeted with drugs, HPV relies almost entirely on the host cell's machinery to replicate. That makes it extremely difficult to develop antivirals—there's no viral-specific target to attack without also damaging normal cells.
Currently, no drugs are approved specifically for clearing HPV infections. Available treatments address symptoms (topical therapies for warts) or remove precancerous tissue surgically. The virus itself often clears naturally through immune responses, but in cases where it doesn't—causing persistent infections that can lead to cervical, throat, and other cancers—options are limited.
A potential breakthrough emerged from the University of New Mexico in February 2025. Researchers formulated trametinib—an FDA-approved drug for melanoma—as a topical gel for cervical dysplasia caused by HPV. The approach targets a cellular signaling pathway that HPV hijacks to drive abnormal cell growth. In animal studies, the gel successfully shrank tumors within eight days of treatment.
The National Cancer Institute awarded a $2.7 million grant to advance the therapy toward human trials expected in 2025-2026. If successful, it would represent the first true antiviral treatment for HPV infections rather than just managing their consequences.
"This is cancer interception," explains the research team in published statements. "We're trying to stop precancerous cells from becoming malignant, rather than treating established cancers."
Frantz Viral Therapeutics is conducting Phase 2 trials of a vaginal insert designed to eliminate abnormal cervical cells and clear HPV infection in women with high-grade dysplasia. Phase 1 results showed 68% clearance of precancerous lesions and 50% tested HPV-negative afterward—potentially offering the first non-surgical option for the 300,000 U.S. women diagnosed annually with high-grade cervical precancers who currently face procedures like LEEP (loop electrosurgical excision).
An unexpected finding published in May 2024 suggests repurposing potential. Case series documented that acyclovir—the common herpes drug—cleared various HPV lesions including genital warts and even large tumorous growths in multiple patients. The mechanism isn't clear since acyclovir targets herpes enzymes that HPV lacks, but researchers hypothesize it may work by affecting the immune microenvironment around HPV lesions. Three randomized controlled trials launched in Egypt in 2024 to test this systematically.
Therapeutic vaccines—designed to treat existing infections rather than prevent new ones—represent the most advanced investigational approach. Over 20 candidates are in development according to a July 2024 WHO report. The most promising include a vaccine from Institut Pasteur that achieved 100% tumor elimination in preclinical animal models, now in early human trials at Moffitt Cancer Center, and multiple mRNA, DNA, and bacteria-based vaccines in Phase 2 trials showing 50-70% regression rates for precancerous lesions.
"The challenge with HPV," one gynecologic oncologist told me, "is that by the time you detect it, the virus has already evaded initial immune responses. These therapeutic vaccines try to restimulate immunity that wasn't effective the first time around."
Respiratory viruses get new weapons and prevention strategies
COVID-19 antiviral development in 2024-2025 focused on addressing the limitations of first-generation drugs. While Pfizer's Paxlovid remains highly effective for high-risk unvaccinated patients, it requires taking ritonavir—a drug interaction nightmare that makes it incompatible with many common medications including statins, immunosuppressants, and cardiovascular drugs. It also causes an unpleasant metallic taste that leads some people to stop taking it.
Pfizer initiated Phase 3 trials in December 2024 of ibuzatrelvir, a second-generation protease inhibitor that eliminates the ritonavir requirement. The cleaner safety profile and once-daily dosing could expand treatment to much broader patient populations currently unable to use Paxlovid safely.
The more significant development came from Shionogi, a Japanese pharmaceutical company whose drug ensitrelvir achieved a world first: FDA acceptance in September 2025 of an application for post-exposure prophylaxis with a decision expected by June 2026. The drug would be taken after exposure to COVID-19—such as by household members of infected people—to prevent infection from developing.
The Phase 3 trial showed a 67% reduction in COVID-19 risk when taken within 72 hours of household exposure: 2.9% of people taking ensitrelvir developed COVID-19 versus 9% with placebo, in a study of over 2,000 participants conducted through 2024. If approved, it would become the first and only oral therapy for COVID-19 prevention following exposure, filling a critical gap for healthcare workers, household contacts, and others in high-exposure situations.
"We learned from COVID that treatment and prevention need to go hand-in-hand," explains one infectious disease specialist. "Having something people can take after exposure—not daily like a preventive medicine, but just when they need it—changes the calculation significantly."
For influenza, a major milestone was achieved with baloxavir marboxil (Xofluza). The drug, already approved for treating flu, demonstrated in a Phase 3 trial published in the New England Journal of Medicine in April 2025 that a single oral dose reduced household transmission by 32%. In the study of nearly 1,500 index patients and 2,681 household contacts across 272 sites globally, infection rates were 9.5% with baloxavir versus 13.4% with placebo.
This represents the first Phase 3 trial to demonstrate that an antiviral can reduce transmission of a respiratory viral illness, not just treat individual infections—a proof-of-concept with major public health implications for outbreak control.
Respiratory syncytial virus achieved perhaps its most significant milestone: the first antiviral with positive Phase 3 results. Shanghai Ark Biopharmaceutical's ziresovir, an oral drug targeting the viral fusion protein, demonstrated statistically significant improvements in infants hospitalized with RSV. Results published in the New England Journal of Medicine showed faster clinical improvement and greater viral load reductions compared to placebo.
The long-term benefits proved even more striking. At 24-month follow-up, infants who received ziresovir had 3.6 times lower rates of recurrent wheezing than those who received placebo. Asthma rates were 3% versus 5%. This represents the first evidence that early antiviral intervention might reduce chronic respiratory sequelae—suggesting RSV drugs could prevent long-term lung disease, not just treat acute infections.
"That long-term data is really the story," notes one pediatric pulmonologist. "We've known RSV causes chronic problems for years. If we can prevent that with early treatment, the public health impact could be enormous."
The WHO included ziresovir on its GAP-f PADO-RSV priority list in July 2025—the first and only antiviral on this pediatric drug priority list. The therapy is under regulatory review in China.
Hepatitis programs inch toward functional cures
Hepatitis B remains one of the major unsolved problems in infectious disease. Current treatments can suppress the virus but rarely eliminate it, leaving patients on lifelong therapy. The challenge lies in the virus's covalently closed circular DNA (cccDNA)—a stable form that persists in liver cells and can reactivate if treatment stops.
Multiple approaches entered clinical trials in 2024-2025 targeting different vulnerabilities. TherVacB, a therapeutic vaccine developed over 12 years, initiated Phase 1b/2a trials in June 2025 in Europe and Africa, designed to induce HBV-specific immunity against over 95% of global strains. An Arbutus Biopharma RNA interference drug called imdusiran, combined with pegylated interferon, achieved 28% sustained loss of the viral surface antigen—a key marker of functional cure—with protective antibody development and no serious adverse events in a study presented at the 2024 European liver conference.
Perhaps most striking: hepalatide, an entry inhibitor that blocks the virus from infecting new liver cells, combined with pegylated interferon achieved 33-40% complete disappearance of cccDNA from liver biopsies in a trial presented at the same conference. That's significant because eliminating cccDNA addresses the root persistence mechanism.
"We're throwing multiple mechanisms at hepatitis B simultaneously," explains one hepatologist familiar with the trials. "The idea is that combinations—like we did with hepatitis C—can achieve cures where single drugs plateau at suppression."
Hepatitis D treatment advanced despite U.S. regulatory challenges. Bulevirtide, which blocks viral entry, received European approval in 2023 and shows strong long-term effectiveness in real-world studies. Phase 3 trials showed 45-48% combined response rates, with even better outcomes when combined with peginterferon. But the drug remains unapproved in the U.S. after receiving a Complete Response Letter from the FDA in 2022, leaving American patients without options while Europeans have access to effective treatment.
Hepatitis C reached a new milestone with the FDA expanding Mavyret approval in June 2025 to become the first drug approved specifically for acute HCV—treating newly acquired infections before they become chronic. The 96% cure rate for acute infections supports "screen and treat" models that could prevent chronic infection before it establishes.
With pan-genotypic direct-acting antivirals now registered in 145 of 160 countries and reimbursed in 109 countries as of mid-2023, hepatitis C has transitioned from incurable to routinely curable—a model the field hopes to replicate for hepatitis B.
Herpes and CMV face new long-acting compounds
Herpes simplex virus treatment is poised for its first major advancement in over 25 years. Assembly Biosciences' ABI-5366, a novel helicase-primase inhibitor, completed Phase 1a trials in 32 healthy participants with excellent tolerability and potentially game-changing pharmacokinetics: a half-life exceeding 20 days that could enable monthly dosing.
This represents a dramatic departure from daily acyclovir or valacyclovir, which most people with genital herpes take indefinitely to prevent outbreaks and reduce transmission risk. The compound is 40 times more potent than acyclovir against HSV-2 and distributes to nerve ganglia where latent virus resides—something current drugs don't do well.
Phase 1b proof-of-concept data is expected in the second half of 2025. If successful, monthly or even less frequent dosing could transform management for the 846 million people globally living with genital herpes by eliminating the adherence challenges of daily medication.
Cytomegalovirus treatment options expanded with maribavir (Livtencity), a UL97 kinase inhibitor approved for resistant/refractory CMV, now being tested head-to-head against standard therapy. The drug offers an alternative mechanism when ganciclovir resistance emerges, though resistance to maribavir itself developed in 10% of patients in a Phase 3 trial—a reminder that all antivirals eventually face resistance challenges.
A large Phase 2/3 vaccine trial initiated in March 2024 is testing whether pre-transplant vaccination can reduce the need for prolonged antiviral therapy in liver transplant recipients, potentially preventing CMV disease through immune enhancement rather than continuous drug treatment.
Epstein-Barr virus remains the major gap among herpes viruses. Despite affecting over 90% of the global population and causing approximately 200,000 cancer-related deaths annually, no FDA or EMA-approved EBV antiviral exists. University of Utah researchers discovered that spironolactone—a common heart failure drug—inhibits EBV replication through an unexpected mechanism, potentially opening repurposing opportunities. But overall, EBV therapeutic development lags far behind other herpes viruses, with most approaches still in early preclinical stages.
AI achieves unprecedented efficiency in drug discovery
When Model Medicines published results from its GALILEO AI platform in January 2025, the numbers seemed too good to be true. The system screened 52 trillion molecules computationally, narrowed to a billion-molecule inference library, and selected 12 compounds for synthesis and testing. All 12 showed antiviral activity in lab tests against hepatitis C and human coronavirus.
A 100% hit rate.
Traditional high-throughput screening typically achieves 1-10% hit rates even with sophisticated filtering. Many AI-assisted approaches do better but still see significant failure rates when moving from computational predictions to actual experiments. A perfect 12-for-12 success rate represents either extraordinary luck or a fundamental improvement in predictive capability.
"This is what people have been promising AI could do for years," one drug discovery researcher not involved with the project told me. "Actually seeing it happen is different than hearing about it theoretically."
The GALILEO platform uses geometric graph convolutional networks—a deep learning architecture that represents molecules as graphs with atoms as nodes and chemical bonds as edges—combined with quantum-enhanced computing that uses quantum circuit Born machines to improve molecular screening efficiency. The chemical structures showed minimal similarity to known antivirals, representing truly novel chemical matter rather than variations on existing drugs.
Insilico Medicine pioneered quantum-enhanced approaches, using hybrid quantum-classical computing to screen 100 million molecules and synthesize 15 promising candidates. Two showed biological activity against KRAS-G12D, a notoriously difficult cancer target. The company reports that quantum methods showed 21.5% improvement in filtering non-viable molecules compared to AI-only models.
Atomwise's AtomNet platform, which screens over 100 million compounds daily using deep learning, achieved area-under-curve scores greater than 0.9 on 57.8% of targets in benchmark databases—representing 10,000-fold improvement in hit rates and 100-fold faster results than traditional screening. For antivirals, Atomwise established a joint venture developing broad-spectrum drugs against flaviviruses including Zika, dengue, and West Nile by targeting conserved protein structures shared across the virus family.
Recursion Pharmaceuticals operates at unprecedented scale with 65 petabytes of biological and chemical data generated through millions of cell experiments per week via robotic automation. The company's November 2024 combination with Exscientia, another AI drug discovery leader, created what may be the industry's largest integrated platform. Recursion's first AI-designed drug, REC-3964 for C. difficile infections, entered Phase 2 as a novel non-antibiotic approach—demonstrating the technology can produce clinical candidates, not just computational predictions.
The investment community validated the approach with Xaira Therapeutics raising $1 billion in Series A funding in April 2024—the largest biotech financing in history. The company is building AI tools for drug discovery and development, with backing from top-tier venture firms signaling mainstream confidence that computational approaches can deliver returns.
The FDA published draft guidance in January 2025 for AI use in drug development, providing regulatory clarity that had been lacking. Over 500 FDA submissions with AI components occurred between 2016-2023, and the 2024 Nobel Prize in Chemistry was awarded for AlphaFold protein structure prediction, underscoring the technology's scientific validation at the highest levels.
"The question isn't whether AI works for drug discovery anymore," one pharma executive told me. "It's how fast we can deploy it at scale and what that means for development timelines and costs."
Broad-spectrum approaches target pandemic preparedness
The most ambitious antiviral strategies don't target individual viruses but entire families—developing drugs that work against threats that don't even exist yet.
Synthetic carbohydrate receptors achieved the most dramatic results. Researchers from City University of New York and UCLA, publishing in Science Advances in August 2025, designed nanoparticles that bind to glycans—sugar molecules on viral surfaces that are far more conserved than rapidly mutating viral proteins. They tested 57 different designs against six deadly viruses: SARS-CoV-1, SARS-CoV-2, MERS-CoV, Nipah, Hendra, and Ebola.
Four designs showed activity across all viruses tested. The lead candidate achieved 90% survival rates in COVID-19 mouse models after a single dose, with zero observed toxicity. The mechanism is virucidal—physically inactivating viral particles by irreversibly binding them and preventing both initial attachment and later infection steps.
"This is the kind of antiviral tool the world urgently needs," said lead researcher Adam Braunschweig in published statements. "If a new virus emerges tomorrow, we currently have nothing to deploy."
The technology is advancing to expanded animal studies with human trials anticipated. If successful, it could provide the first true broad-spectrum antiviral capable of addressing pandemic threats across multiple viral families—the pharmaceutical equivalent of broad-spectrum antibiotics, but for viruses.
Other broad-spectrum approaches are progressing through development. PIKfyve inhibitors disrupt endosomal trafficking that multiple viruses require, showing activity against SARS-CoV-2 variants, influenza, and RSV in lab studies and early clinical trials. The peptide P9R, derived from mouse β-defensin-4, demonstrated activity against SARS-CoV, MERS-CoV, SARS-CoV-2, multiple influenza strains, and human rhinovirus without any drug-resistant viruses emerging after 40 serial passages—the gold standard test for resistance potential.
Galidesivir, an adenosine analog targeting viral RNA polymerases, showed activity against MERS-CoV, SARS-CoV, influenza, RSV, and human rhinovirus in preclinical studies. Multiple Phase 1 trials assessed safety, with the advantage that polymerases are more conserved than surface proteins, making pan-viral activity more feasible.
The READDI-SAS partnership, funded by North Carolina's government and academic institutions, represents a new paradigm: maintaining a ready arsenal of Phase 2-ready candidates against high-risk viral families before pandemics occur. The program integrates advanced analytics with machine learning for patient data analysis and causal AI for clinical trial design.
"The traditional model is reactive—a virus emerges, we start developing drugs, and by the time they're ready, the outbreak may be over," explains the program's leadership. "We're trying to flip that by having candidates ready to deploy immediately when novel pathogens emerge."
The NIH's Antiviral Program for Pandemics explicitly aims to develop safe, effective oral antivirals for home use targeting SARS-CoV-2 and five viral families with pandemic potential: coronaviruses, paramyxoviruses, bunyaviruses, picornaviruses, and filoviruses. The goal is to compress development timelines so drugs can be deployed within the WHO's "100 Days Mission"—getting medical countermeasures from pathogen identification to distribution in just over three months.
Investment flows toward platform technologies over single assets
The antiviral market reached $60-65 billion in 2024, projected to grow steadily to $69-85 billion by 2030-2035—moderate but consistent expansion driven by pandemic preparedness investment, increasing disease prevalence, and technological advancement.
But the investment landscape tells a more nuanced story. No novel antiviral drugs were approved among the 50 drugs gaining FDA approval in 2024—a notable gap indicating the field remains in development mode rather than commercialization for truly new molecular entities. Regulatory activity focused on expanded indications for existing drugs: Mavyret's expansion to acute hepatitis C, Paxlovid's full approval following emergency authorization, and similar life-cycle management.
Xaira Therapeutics' $1 billion Series A in April 2024—the largest biotech financing in history—signals where capital is flowing: platform technologies with broad applicability rather than single-asset programs with binary outcomes. Formation Bio raised $372 million in 2024 for AI-based workflow automation. Multiple AI drug discovery companies secured nine-figure rounds while traditional antiviral programs struggled for funding.
"Investors learned from COVID that platforms scale and single assets don't," one venture capitalist told me on background. "If you're building AI that can address multiple pathogens, you get premium valuations. If you're developing one drug for one virus, you need massive clinical data to attract capital."
Geographic distribution shows North America holding 32% market share dominated by U.S. healthcare spending and R&D investment, Europe at 20.7%, and Asia-Pacific as the fastest-growing region at 6.12% compound annual growth. China represents the most lucrative market for expansion, with Japan second.
Major players include Gilead Sciences dominating HIV, COVID-19, and hepatitis C development; GlaxoSmithKline/ViiV Healthcare in HIV; AbbVie in HIV and hepatitis C; Pfizer and Merck in COVID-19; plus Roche/Genentech, Johnson & Johnson, Novartis, and Bristol-Myers Squibb maintaining diversified infectious disease portfolios.
The concentration among large pharmaceutical companies contrasts sharply with innovation driven largely by small biotechs—creating merger and acquisition opportunities. Gilead acquired CymaBay for $4.3 billion in March 2024. Bristol Myers Squibb acquired RayzeBio for $4 billion in February 2024. Fourteen immunology-focused buyouts exceeded $50 million in 2024, indicating therapeutic area preferences shifting toward immune modulation.
Government funding remains critical despite being substantially underfunded compared to vaccine development. BARDA contracts support pandemic preparedness antivirals. NIH's Antiviral Program for Pandemics provides discovery through IND-enabling funding. However, proposed NIH budget cuts of 40% threaten momentum precisely when technologies reach clinical readiness—a concerning disconnect between stated pandemic preparedness priorities and actual resource allocation.
"There's a lot of talk about being ready for the next pandemic," one NIH-funded researcher told me. "But if you cut the budgets supporting the science that creates readiness, it's just talk."
The road ahead: From reactive to proactive
The antiviral field is attempting something unprecedented: building tools to address pandemics before they occur rather than scrambling to develop treatments after outbreaks begin.
Current surveillance focuses on H5N1 avian influenza demonstrating worrying characteristics including transmission in U.S. cattle herds since 2022, mpox prompting a WHO public health emergency declaration in August 2024, measles resurgence as vaccination rates decline, and continuing COVID-19 variant evolution requiring variant-proof therapies.
The WHO pandemic agreement and International Health Regulations amendments adopted in May 2025 establish global frameworks for prevention, preparedness, and response with equity provisions intended to ensure developing countries access therapeutics rather than being last in line as occurred with COVID-19 vaccines and treatments.
Technology trends converging include broad-spectrum antivirals targeting conserved structures across viral families, long-acting formulations enabling weekly to yearly dosing for chronic infections, gene editing transitioning from proof-of-concept to clinical validation, AI drug discovery achieving unprecedented efficiency, and combination therapies addressing resistance through synergy.
Novel mechanisms under investigation include CRISPR/Cas antiviral systems for permanently eliminating viral genomes, antiviral peptides targeting entry and fusion, immunomodulators enhancing innate and adaptive immunity, and host-directed therapies that viruses cannot easily develop resistance against since they target human proteins rather than viral ones.
The strategic question facing the field isn't whether these technologies work—clinical validation is accumulating rapidly. It's whether investment, regulatory frameworks, and global cooperation can keep pace with scientific capability. The COVID-19 experience demonstrated both what's possible with coordinated effort and massive resources, and what happens when preparedness is neglected until crisis hits.
"We have a brief window where the world still remembers COVID-19 and cares about pandemic preparedness," one public health official told me. "In five or ten years, that urgency will fade. The question is whether we build the infrastructure and develop the tools while we still have the political will and resources to do it."
For the 39.9 million people living with HIV, the 1.3 million dying annually from hepatitis, and the billions at risk from the next pandemic, that question isn't academic. It's the difference between incrementally better management of chronic diseases and potentially eliminating them altogether, between developing treatments after the next outbreak spreads globally and having them ready to deploy immediately.
The technological pieces are falling into place. The scientific breakthroughs are accelerating. What remains uncertain is whether the investment, policy, and global cooperation can match the pace of innovation—or whether another pandemic will arrive before we've built the tools to stop it.
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
