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Beyond Processing: Furin as a Central Hub in Viral Pathogenesis and Genetic Susceptibility
Adrián Alejandro Silva-Ríos1, Carlos Ernesto Mora-Ornelas2,3, Luna Galilea Flores-Medina1
1Licenciatura en Médico Cirujano y Partero, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Col. Independencia, Guadalajara 44340, Mexico.
None:
Furin, a calcium-dependent serine endoprotease of the proprotein convertase family, plays a pivotal role in both physiological homeostasis and viral pathogenesis. By cleaving polybasic motifs within viral glycoproteins, furin enables the maturation of structural proteins essential for viral entry, fusion, and replication. This mechanism has been documented across a broad spectrum of human pathogens, including SARS-CoV-2, influenza virus, human immunodeficiency virus, human papilloma virus, hepatitis B virus, flaviviruses, herpesviruses, and paramyxoviruses, highlighting furin as a conserved molecular hub in host-virus interactions. Genetic variability within the FURIN gene further modulates infection outcomes. Several single-nucleotide polymorphisms (SNPs), such as rs6226 and rs1981458, are associated with altered COVID-19 severity, whereas variants like rs17514846 confer protection against human papilloma virus infection. Conversely, mutations predicted to reduce enzymatic activity have been linked to attenuated SARS-CoV-2 pathogenesis in certain populations. These findings underscore the importance of considering population genetics when evaluating viral susceptibility and disease progression. Despite advances, unresolved questions remain regarding furin's non-canonical roles in viral life cycles, tissue-specific regulation, and interactions with other host proteases and immune modulators. Targeted inhibition of furin and related convertases represents a promising avenue for broad-spectrum antiviral interventions. Collectively, current evidence positions furin as a central node at the intersection of viral pathogenesis, host genetic variability, and translational therapeutic potential.
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