MERS-coronavirus spike protein: Importance of protease cleavage sites for viral entry

What is it about?

The spike (S) protein of Middle East respiratory syndrome coronavirus (MERS-CoV) mediates viral entry into host cells. For this, MERS-S depends on processing by host cell proteases and two cleavage sites have been identified: The first one, termed S1/S2 site, is located between the surface unit S1 and the transmembrane unit S2. The second one is located in the S2 subunit and is termed S2’ site. We found that an intact S1/S2 site is only required for entry when S protein cleavage depends on the host cell protease TMPRSS2. In contrast, an intact S2’ site was universally required, irrespective of whether the S protein was cleaved by TMPRSS2 or the endosomal cysteine protease cathepsin L.

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Why is it important?

Our results show that TMPRSS2 cleaves MERS-S at the S2’ site and confirm the concept that precleavage at S1/S2 is required for subsequent cleavage and activation by TMPRSS2.

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