Tmprss2: A Key Host Factor In SARS-CoV-2 Infection And Potential Therapeutic Target

The TMPRSS2 gene is crucial for SARS-CoV-2 infection as it primes the viral spike protein for membrane fusion, facilitating viral entry into host cells. This review highlights TMPRSS2's role in COVID-19, noting its high expression in lung and prostate tissues and regulation by androgens, which may explain sex-based differences in disease severity. Genetic polymorphisms in TMPRSS2 affect disease susceptibility and severity. Inhibitors like camostat mesylate and nafamostat show promise in blocking viral entry, while RNA-based strategies offer potential for downregulating TMPRSS2 expression. Challenges remain in developing selective inhibitors without off-target effects. The TMPRSS2-ERG gene fusion, common in prostate cancer, is linked to altered COVID-19 susceptibility, indicating a complex relationship between viral infection and cancer. Future directions include genomic studies to identify high-risk individuals and developing next-generation TMPRSS2 inhibitors and broad-spectrum antiviral therapies.