An international research team has gained new insights into the way SARS-CoV-2 enters cells and its downstream consequences. As an aid to the ACE2 surface protein, the TMPRSS2 serine protease plays an important role in enhancing cell infection: it boosts the resulting immune response, increases cell death, and drives virus evolution. In addition to the human version, TMPRSS2 proteins from diverse mammal species can also enhance infection. These findings may contribute to the development of future treatments and prevention strategies. Proceedings of the National Academy of Science (PNAS) reports on these results in its edition from 4 June 2024.