Host-directed antiviral strategies: Repurposing dsRNA viruses for broad-spectrum pandemic preparedness

The COVID-19 pandemic exposed the fragility of pathogen-specific antiviral strategies and the urgent need for immediately deployable, broad-spectrum solutions. The current Ebola epidemic, now widely described as escalating beyond containment, has made that gap acutely visible once again. While vaccines and targeted antivirals remain essential, their development is slow, costly, and reactive, leaving populations exposed during the critical early weeks of an outbreak. Host-directed therapies that harness innate immunity offer a practical alternative. Infectious Bursal Disease Virus (IBDV), an orally administered, attenuated avian dsRNA vaccine virus, has demonstrated broad antiviral activity in hepatitis A (marmosets) and hepatitis B and C, COVID-19 and herpes zoster patients, has a strong interferon-inducing capacity, carries a safety record established across billions of poultry vaccinations, and has already undergone positive evaluation by NIH ACTIV. It is not a theoretical construct, but an existing public-good antiviral technology that has yet to be seriously evaluated for emergency human use.

The goal of this Research Topic is to catalyse a paradigm shift in pandemic preparedness by highlighting the potential of IBDV as a safe, scalable, and immediately deployable antiviral. Veterinary IBDV vaccine has been commercially available for more than 60 years and is genetically equivalent to the reverse-engineered human drug candidate (IBDV R903/78), positioning it as a pragmatic stop-gap that could be deployed under emergency or compassionate use frameworks while formal registration proceeds. Because live vaccines confer beneficial immune training that lowers overall mortality and morbidity, the nonspecific effects of vaccines also call for revision of how new vaccines are tested, approved, and regulated. The central question this forum poses is not whether a new antiviral should be developed, but what rapid, scientifically grounded steps regulators and researchers could take with the tools already in hand.

We invite contributions that advance this discussion, with an emphasis on actionable analysis and expert debate. Areas of interest include:
• Rapid-response pathways for deploying existing host-directed antiviral platforms during active outbreaks, including the current Ebola epidemic
• Mechanisms of innate immune activation by dsRNA viruses and viral interference
• Clinical and preclinical evidence of live vaccine efficacy across multiple viral families
• Comparative analyses of host-targeted versus pathogen-specific antiviral approaches
• Regulatory and ethical frameworks for emergency or compassionate use of veterinary-origin vaccines in humans
• Revising testing and approval frameworks to account for the nonspecific effects of live vaccines
• Integration of One Health principles into pandemic preparedness planning
• Strategies for scaling, stockpiling, and equitable distribution of broad-spectrum antivirals



Topic Editor, Dr. Tibor Bakacs, declares stock/stock options from HepC Inc., and he is also a shareholder of HepC Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.