The Antiviral Nanotechnology Gap in COVID-19: Systematic Barriers to Pandemic-Scale Translation and Deployment

Abstract

For over two decades, antiviral nanotechnologies have demonstrated robust preclinical efficacy against diverse viral pathogens, including coronaviruses. Yet during the COVID-19 pandemic, these platforms contributed minimally to the global therapeutic response despite unprecedented urgency, regulatory flexibility, and funding availability. This narrative review, structured using the DELIVER framework (Joyce et al., 2024), systematically analyses the translational barriers that constrained deployment across scientific, regulatory, manufacturing, economic, and institutional domains.
A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar (January 2000-December 2024), supplemented by ClinicalTrials.gov and regulatory policy documents. Following deduplication and eligibility screening of 2,847 records, 90 peer-reviewed articles were included in the qualitative synthesis (inter-rater agreement: Cohen's kappa = 0.88). Only three systemic antiviral nanotechnology trials were identified during COVID-19, none of which achieved regulatory authorisation. In contrast, mRNA-lipid nanoparticle (LNP) vaccines succeeded because of long-term pre-pandemic platform maturation, established manufacturing partnerships, early regulatory engagement, and coordinated government support through Operation Warp Speed (~$18 billion).
Key barriers included manufacturing complexity, regulatory pathway ambiguity, absent pandemic-ready production capacity, fragmented intellectual property landscapes, and weak cross-sector coordination. Crucially, these barriers did not operate independently but formed mutually reinforcing cascades that rendered single-domain interventions insufficient. Partial successes--including diagnostic nanoparticle platforms and liposomal oncology reformulations--demonstrate that context-specific enabling factors, rather than inherent technological limitations, largely determined translation outcomes. Advancing antiviral nanotechnologies for future pandemics requires proactive, inter-pandemic investment in scalable manufacturing, clearer regulatory frameworks, platform-based development strategies, and coordinated economic instruments. This principally US-focused analysis offers policy insights applicable across high-income country (HIC) and, selectively, lower-middle-income country (LMIC) settings.