A virus mutates, an antiviral loses potency, and a new outbreak finds us one step behind. This cycle has defined antiviral medicine for decades. Now, a convergence of broad-spectrum drug design, host-targeted therapies, AI-driven discovery, nanotechnology, and CRISPR gene editing is starting to shift the field from reactive to anticipatory, though each approach brings its own unresolved challenges.
Why Current Antivirals Fall Short
The COVID-19 pandemic exposed how narrow the existing antiviral arsenal really is. Over 700 million confirmed cases and millions of deaths later, the economic burden is estimated at tens of trillions of pounds globally (not including long COVID). Most approved antivirals target a single virus or viral family, which works until resistance mutations emerge or a novel pathogen arrives.
The antiviral drug market is projected to reach USD 96.30 billion by 2032, growing at 5.3% annually (Coherent Market Insights), driven in part by investment in AI, nanotechnology, and gene editing. That growth reflects a broader recognition: we need drugs that work across viral families, therapies that strengthen host defences rather than chasing every new variant, and discovery pipelines fast enough to respond before an outbreak becomes a pandemic.
Broad-Spectrum Antivirals
Broad-spectrum antivirals (BSAs) target mechanisms conserved across multiple viruses, including viral entry, replication machinery, and host-cell interactions, offering a first line of response when a new pathogen emerges. Because these targets are shared, BSAs carry a lower risk of resistance, though this advantage is not absolute.
Synthetic Carbohydrate Receptors (SCRs)
Many pathogenic enveloped viruses (coronaviruses, filoviruses, paramyxoviruses) coat their surface glycoproteins with N-glycans that are highly conserved across families, even as the underlying proteins mutate rapidly. These glycans are essential for host-cell attachment, membrane fusion, and immune evasion. SCRs bind to these envelope N-glycans, blocking attachment and preventing fusion at an early stage of infection.
A 2025 study in Science Advances screened 57 SCRs against pseudotyped virus particles from seven high-risk enveloped viruses across three families: Coronaviridae (SARS-CoV-2, SARS-CoV-1, MERS-CoV), Filoviridae (Ebola, Marburg), and Paramyxoviridae (Nipah, Hendra). Four SCRs inhibited all tested viruses, and two leads were validated against live virus. In a severe SARS-CoV-2 mouse model, a single intranasal dose achieved 90% survival compared to none in the control group.
Sulphur-Containing Compounds
Small molecules with functional sulphur groups (thiols, disulfides, thioethers, sulfones, acyl disulfides) show broad-spectrum activity against enveloped viruses including influenza and SARS-CoV-2. They work by disrupting viral membranes, reducing disulfide bonds in viral surface proteins, or generating reactive sulphur species. In influenza models, one compound series (XM) enhanced the efficacy of inactivated vaccines, suggesting a combined prophylactic and therapeutic role.
Drug Repurposing
Screening existing approved drugs for antiviral activity remains one of the fastest routes to the clinic. A 2025 computational study identified phenformin and Atpenin A5 as replication inhibitors across influenza, mpox, and SARS-CoV-2. These compounds work not by targeting the virus directly, but by blocking mitochondrial metabolism in host cells.
Host-Targeted Antiviral Therapies
Host-targeted antivirals (HTAs) modulate human proteins that viruses exploit. Because viruses cannot easily mutate around a host target, HTAs tend to offer broader activity and a lower resistance risk than direct-acting antivirals.
A 2025 review catalogued HTAs for SARS-CoV-2 targeting entry factors such as TMPRSS2 and endosomal pathways. One established example is fostemsavir, approved in 2020 for HIV, which locks the gp120 subunit into a conformation that prevents binding to CD4 receptors. In respiratory viruses, Fludase (DAS181) has reached clinical trials for influenza and parainfluenza, cleaving sialic acid residues from cell surfaces to remove the receptors these viruses need.
PROTACs
Proteolysis Targeting Chimeras (PROTACs) destroy specific disease-causing proteins inside cells rather than just inhibiting them. They use a three-component structure: one end binds the target protein, the other recruits an E3 ubiquitin ligase, and a linker holds them together. The ligase tags the target with ubiquitin chains, marking it for degradation by the 26S proteasome. No antiviral PROTACs have reached the market, but preclinical research is ongoing for HCMV, influenza, and SARS-CoV-2.
Immune Modulation and Membrane Targeting
Anakinra, an IL-1 receptor antagonist, was repurposed during the COVID-19 pandemic and shown to reduce inflammation during the cytokine storm stage. Another emerging strategy targets sphingomyelin synthesis, inhibiting the enzymes that produce sphingomyelin, a lipid that enveloped RNA viruses co-opt during host membrane hijacking. This has shown effectiveness against SARS-CoV-2, influenza, and Dengue in preclinical models.
AI in Antiviral Drug Discovery
AI is compressing drug discovery timelines from years to months, though it has not eliminated the need for wet-lab validation. During the early COVID-19 response, BenevolentAI identified baricitinib, a rheumatoid arthritis drug, as a potential inhibitor of viral entry via clathrin-mediated endocytosis, a prediction subsequently validated in clinical trials and published in The Lancet.
For enterovirus 71 (EV71), a machine learning system trained on 36 small molecules produced a shortlist of eight candidates. Five slowed viral replication, a hit rate roughly ten times what conventional screening would deliver. ML models are also being used to predict drug efficacy against emerging SARS-CoV-2 variants, offering a way to stay ahead of viral evolution rather than responding to it after the fact.
Nanotechnology
Nanoscale materials (1 to 100 nm) address several limitations of conventional antiviral delivery: poor solubility, low bioavailability, rapid clearance, and off-target side effects.
Direct viral inactivation. Silver nanoparticles release Ag⁺ ions that damage viral genetic material and block host-cell entry, with inhibitory activity demonstrated against SARS-CoV-2, influenza H1N1, and HIV-1.
Drug delivery. Nanoparticles encapsulate antiviral drugs, protecting them from degradation and enabling controlled release at infection sites. Lipid nanoparticles already play an established role here; they enabled the mRNA delivery platform behind the COVID-19 vaccines.
Immune modulation. Certain nanomaterials, including lipid nanoparticles, metallic nanoparticles, and virus-like particles, mimic viral structures to stimulate innate immune responses. They also enhance adaptive immunity by improving antigen delivery and acting as vaccine adjuvants.
Biomimetics. Nanoparticles can be engineered to resemble cell surfaces or viral structures, trapping viruses without harming host cells. Biomimetic glycodendriprotein nanoparticles that mimic Ebola’s glycosylated envelope proteins have inhibited viral attachment at picomolar to nanomolar concentrations.
Antiviral surfaces. Copper nanoparticle coatings inactivate SARS-CoV-2 within 1 hour, considerably faster than bulk copper, through Cu²⁺ ion release, ROS generation, and envelope disruption. Photoactive titanium dioxide (TiO₂) nanoparticles achieve inactivation rates up to 99.96% against influenza and SARS-CoV-2 upon exposure to UV or visible light, and are already used in paints, door handles, and hospital surfaces.
CRISPR Gene Editing
CRISPR originated as a bacterial immune system: when a virus attacks, the bacterium saves a snippet of viral DNA as a molecular “memory”, then uses the Cas9 protein to find and cut that DNA if it reappears. Researchers repurposed this system in the 2010s, designing custom guide RNAs to direct Cas9 to virtually any location in a genome. Once cut, the cell’s repair machinery can disable a gene, correct a mutation, or insert new instructions.
CRISPR antiviral systems are not yet available clinically, though treatments for genetic conditions, such as the sickle cell therapy Casgevy, have set a precedent for therapeutic gene editing in humans.
Two CRISPR antiviral programmes have reached clinical trials. EBT-101, designed to excise integrated HIV proviral DNA, was safe and well tolerated, but the virus rebounded in all participants who stopped antiretroviral therapy, indicating incomplete clearance of the latent reservoir. CRMA-1001, developed by nChroma Bio, uses CRISPR-derived technology differently: rather than cutting DNA, it acts as an epigenetic silencer, methylating both covalently closed circular DNA (cccDNA) and integrated hepatitis B DNA to durably suppress viral replication. The first patient was dosed on 28 January 2026, with clinical trial authorisations in Hong Kong, the UK, and New Zealand.
The Path Ahead
Broad-spectrum drugs, host-targeted therapies, AI-accelerated discovery, nanoscale delivery, and CRISPR-based approaches each address a different failure point in the traditional antiviral model. Together, they represent a shift from chasing individual viruses after they emerge to building preparedness across viral families.
The challenges are substantial: delivery, off-target effects, toxicity, maturing regulatory pathways, and the 5 to 10 years typically required to translate preclinical promise into approved treatments. Whether these approaches will prevent the next pandemic is an open question. What they are already doing is changing the terms of the conversation, from “which virus will catch us off guard?” to “how broadly can we prepare?”
How VRS Can Help
Many of these emerging strategies, from broad-spectrum compounds to nanomaterial-based agents, require rigorous in vitro testing before they can progress to clinical development. At VRS, we offer antiviral drug screening services using high-content imaging, IC50 determination, and multiple assay formats across a wide panel of viruses. We also provide industrial antiviral testing to ISO and ASTM standards for surface coatings, textiles, and liquid formulations. If you’re developing a novel antiviral compound, surface treatment, or delivery system, get in touch to discuss how we can support your research.
References
- World Health Organization. COVID-19 Dashboard. https://covid19.who.int/
- Ezzatpour S, Thakur K, Ndede KE, et al. Broad-spectrum synthetic carbohydrate receptors (SCRs) inhibit viral entry across multiple virus families. Science Advances. 2025;11(35):eady3554. doi: 10.1126/sciadv.ady3554
- Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. The Lancet. 2020;395(10223):e30-e31. doi: 10.1016/S0140-6736(20)30304-4
- Excision BioTherapeutics. Data from the Phase 1/2 trial of EBT-101 in HIV and in vivo efficacy data in herpes virus and hepatitis B. Presented at: 27th ASGCT Annual Meeting; May 2024; Baltimore, MD. https://www.excision.bio/news/press-releases/detail/43/excision-biotherapeutics-announces-data-from-the-phase-12
- nChroma Bio. First patient dosed in Phase 1/2 clinical trial of epigenetic silencer CRMA-1001 for chronic hepatitis B. Press release, 28 January 2026. https://www.nchromabio.com/press-release/first-patient-dosed-in-phase-1-2-clinical-trial/
- Coherent Market Insights. Antiviral Drugs Market Size, Share & Growth Analysis, 2025-2032. https://www.coherentmarketinsights.com/market-insight/antiviral-drugs-market-4912
