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Nsp1 facilitates SARS-CoV-2 replication through calcineurin-NFAT signaling

Lui et al., Virology, doi:10.1128/mbio.00392-24

Feb 2024

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In Vitro study showing cyclosporine A (CsA) and the calcineurin-NFAT inhibitor VIVIT inhibit SARS-CoV-2 infection in lung epithelial Calu-3 cells. Authors find SARS-CoV-2 protein Nsp1 hijacks host NFAT signaling by binding calcineurin A, displacing regulator RCAN3 to drive NFAT activation. This induces DEAD-box helicase DDX5 to facilitate viral replication. Combining CsA or VIVIT with SARS-CoV-2 protease inhibitor nirmatrelvir shows synergistic antiviral effects. The results suggest targeting NFAT-DDX5 pathways may mitigate SARS-CoV-2 infection, while calcineurin inhibitors could enable protease inhibitor treatment for immunosuppressed patients.

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Lui et al., 27 Feb 2024, peer-reviewed, 8 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

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