TMPRSS2 in microbial interactions: Insights from HKU1 and TcsH.

Transmembrane Serine Protease 2 (TMPRSS2), known primarily for its role as a protease, has emerged as a critical receptor for microbial agents such as human coronavirus HKU1 and exotoxin TcsH. HKU1 utilizes both sialoglycan and TMPRSS2 for cellular entry, where sialoglycan primes the spike protein for TMPRSS2 binding. TMPRSS2 undergoes autocleavage to enhance its affinity for the HKU1 spike, facilitating viral membrane fusion postcleavage. Interestingly, TMPRSS2's catalytic function is dispensable for both HKU1 and TcsH interactions, suggesting alternative roles in pathogenesis. Structural insights highlight potential therapeutic targets against viral infections and cancers, leveraging TMPRSS2 interactions for drug development. Understanding the interplay between TMPRSS2 and microbes opens new avenues for targeting TMPRSS2 in developing treatments for infections.