Trends, Gaps, and Challenges in Antiviral Resistance: A Bibliometric Analysis and Narrative Synthesis of Key Viruses, Resistance Mechanisms, and Drivers.

Abstract

Ribonucleic acid (RNA) viruses mutate faster than bacteria and most DNA viruses, yet our understanding of mutation-induced viral resistance remains limited compared with bacterial resistance. This has resulted in a fragmented global research landscape on antiviral resistance. This study is aimed at providing a holistic understanding of the global research landscape of antiviral resistance using bibliometric approach and narrative synthesis. Both PubMed and Scopus database was systematically searched following the Scientific Procedures and Rationales for Systematic Literature Reviews (SPAR-4-SLR) protocol. Scopus yielded 375 records, whereas PubMed yielded 100 documents, all of which completely overlapped with those retrieved from Scopus. Given this overlap, the final dataset from Scopus (n = 314) was analyzed using VOSviewer, Biblioshiny, and R to identify publication trends, keyword evolution, author productivity, institutional contributions, and collaborative networks. Additionally, key findings from the Top 20 most cited studies and research on resistance mechanisms were synthesized to highlight research gaps. A total of 314 documents published between 1991 and 2026 (March 23, 2026) across 194 sources were identified, showing a modest annual growth rate of 2%. Research output peaked in 2020, although citation patterns were inconsistent. Keywords were dominated by pathogens such as human immunodeficiency virus (HIV), influenza, and COVID-19, indicating a focus on pathogen. Publications were concentrated in a limited number of high-impact journals (28.03%) and led predominantly by institutions in high-income countries, especially the United States. Mechanistically, resistance primarily arose from mutations in viral enzymes, with major drivers, including poor adherence, suboptimal dosing, prolonged therapy, misuse of antivirals, and intrinsic viral mutation rates. It is important to note that the mandatory inclusion of One Health-related terms in the search strategy may have excluded relevant antiviral resistance publications that did not explicitly utilize the One Health framework, potentially limiting the comprehensiveness of the retrieved literature. Antiviral resistance research within the One Health framework remains limited, narrowly focused, and geographically concentrated. Broader, interdisciplinary studies and enhanced global research capacity are urgently needed to address existing knowledge gaps and disparities.