Furin as a Novel Pan-Viral Therapeutic Target: Implications for Dengue and SARS-CoV-2.

Dengue virus (DENV) and SARS-CoV-2 are emerging viral pathogens that share overlapping clinical features, including fever, fatigue, and respiratory symptoms, complicating differential diagnosis in endemic regions. Their co-circulation has increased the risk of co-infections, which may result in unpredictable disease progression, increased morbidity, and mortality. This overlap presents a significant challenge in managing outbreaks, as both viruses pose a major public health threat. Vaccines and direct-acting antivirals may be rendered ineffective by viral mutations, making it difficult to address evolving strains. Host-directed antivirals offer a promising alternative, potentially maintaining efficacy against a multitude of variants. Both DENV and SARS-CoV-2 rely on host proteases for viral maturation and entry, with furin playing a crucial role in viral glycoprotein cleavage. In DENV, furin cleaves the prM protein, facilitating virion maturation, while in SARS-CoV-2, the polybasic furin cleavage site in the spike protein enhances viral entry. This makes furin a compelling pan-viral target, where inhibiting furin could reduce viral fitness without relying on viral mutations. This review highlights the therapeutic rationale for targeting furin and discusses luteolin, a furin inhibitor showing antiviral activity against both viruses. Furin-targeted therapies may offer a durable antiviral strategy effective across DENV serotypes, SARS-CoV-2 variants, and co-infection settings.