A newly published study reveals how feline coronavirus (FCoV) cleverly exploits host proteases to ensure efficient infection of intestinal cells 🧫🐱. Rather than relying on a single activation pathway, FCoV shows remarkable flexibility in spike (S) protein activation, adapting to the local proteolytic environment of the gut.

Through an extensive protease screen, the team identified serine proteases as key drivers of FCoV infection ⚙️✨. Pancreatic proteases such as trypsin, chymotrypsin, and elastase strongly enhanced infection and syncytia formation—despite their different cleavage preferences—pointing to a highly adaptable viral strategy. Membrane-bound proteases TMPRSS2 and TMPRSS11D further contributed in a strain-dependent manner 🔄.

Importantly, the study experimentally confirms the S1/S2 and S2′ cleavage sites on the FCoV spike protein and uncovers additional sites 🧩🔍. A standout finding is a compensatory cleavage mechanism at the S2′ site, preserving spike activation even when canonical motifs are disrupted—highlighting the central role of S2′ in viral entry 🚪💥. An acidic microenvironment was also shown to be essential for efficient infection ⚠️⬇️.

👏📊 Altogether, this work provides powerful insights into coronavirus adaptability and host–virus interactions, offering broader relevance for spike activation mechanisms across coronaviruses.

🔗 A must-read for anyone interested in virology, protease biology, and viral entry mechanisms!

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