Interplay between the arachidonic acid/cyclooxygenase 2/prostaglandin E2 pathway and RNA viral infections.

INTRODUCTION Viruses manipulate cellular pathways to support their replication, often leading to inflammatory responses through the arachidonic acid (AA)/cyclooxygenase (COX)/prostaglandin E2 (PGE2) axis. Given the potential impact of this pathway on viral pathogenesis and disease severity, defining its role during infection warrants attention. AREAS COVERED This review examines the roles of COX-2 and its primary metabolite, PGE2, in RNA virus infections, highlighting their context-dependent effects on viral replication, pathogenesis, and host immunity. It also covers the therapeutic potential of selective COX-2 inhibitors over these processes. The review is based on articles retrieved during 2000-2025 through a systematic search in PubMed and the web. EXPERT OPINION Emerging evidence suggests that the AA/COX-2/PGE2 axis exerts significant, yet context-dependent antiviral effects during RNA virus infections. Critical gaps remain in understanding the tissue-specific effects of this pathway during RNA virus infections, including the contributions of COX-2-derived metabolites and their molecular mechanisms of action. In vivo studies and clinical trials are needed to evaluate the therapeutic potential of targeting the AA/COX-2/PGE2 axis, with available safe COX-2-inhibiting drugs approved for human use that allow such approaches. Knowledge derived from these assays could yield impactful therapeutic applications that significantly improve clinical outcomes in RNA virus infections.