The loss of measles elimination status in Canada—and by extension across North America1—underscores a sobering reality: vaccination alone no longer guarantees global protection against viral threats. Rising vaccine hesitancy and disrupted immunisation programmes threaten decades of progress in controlling respiratory pathogens. In this shifting landscape, antivirals offer an essential complementary approach. However, virus-specific drugs require enormous time and cost, as seen during the initial years of the COVID-19 pandemic, often with minimal success. Broad-spectrum antivirals represent a promising alternative; however, none are currently in routine clinical use. In earlier correspondence to The Lancet,2 we highlighted host-targeting iminosugars as broad-spectrum antivirals in vitro and in animal models, although clinical development remains incomplete. These compounds inhibit endoplasmic reticulum-resident glucosidases, disrupting viral glycoprotein maturation essential for replication across diverse viruses.3 Evidence includes activity in animal models of hepatitis B and C, Japanese encephalitis, influenza,4 and dengue,5 and in vitro efficacy against HIV (including multidrug-resistant strains) and all SARS-CoV-2 variants. Since our 2022 publication,2 the novel agent MON-DNJ has shown efficacy against major SARS-CoV-2 strains, measles, and respiratory syncytial virus, highlighting its potential as a pan-respiratory antiviral targeting viruses most likely to cause pandemics. Emerging evidence suggests a mechanistic explanation for sustained antiviral activity: activation of the unfolded protein response. By inhibiting glucosidases 1 and 2, iminosugars such as MON-DNJ6 might induce endoplasmic reticulum stress through misfolded glycoprotein accumulation, triggering the unfolded protein response—a stress pathway typically suppressed by enveloped viruses to maintain access to the host glycosylation machinery.6 Pharmacological activation of the unfolded protein response creates a prolonged intracellular environment hostile to viral replication, extending efficacy beyond the drug's pharmacokinetic window. This mechanism could explain observed success in animals infected with influenza or dengue after a single high-dose administration of MON-DNJ.5 A one-dose or two-dose regimen offers a practical, scalable intervention during outbreaks, especially when funding is scarce. Safety remains paramount. Miglustat—a close relative of MON-DNJ—has been approved since 2002 for Gaucher's disease and is used daily by thousands without major side-effects, providing a precedent for the therapeutic viability of host-targeting iminosugars.7 However, MON-DNJ urgently requires completion of clinical development. Unlike vaccines, which require time and widespread uptake, unfolded protein response-inducing antivirals could be deployed immediately, even in populations with high vaccine hesitancy. Investing in host-targeting antivirals such as MON-DNJ, which are administered orally and do not require a cold chain, could save countless lives and position the UK as a global leader in pandemic preparedness. There is not only a scientific and strategic imperative but also a moral one: to ensure effective, scalable antiviral solutions if vaccination programmes face resistance and delays during new epidemics. We urge renewed investment in host-targeting antivirals—not only for existing viruses such as measles, respiratory syncytial virus, and dengue, but also as strategic tools for future pandemics. MON-DNJ opens a new frontier in antiviral pharmacology, offering a paradigm shift that could transform global responses and prevent the catastrophic losses seen during the COVID-19 pandemic.