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'publisher': 'American Society for Microbiology',
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'abstract': '<jats:title>ABSTRACT</jats:title>\n'
' <jats:sec>\n'
' <jats:title />\n'
' <jats:p>SARS-CoV-2, the causative agent of COVID-19, has been intensely studied '
'in search of effective antiviral treatments. The immunosuppressant cyclosporine A (CsA) has '
'been suggested to be a pan-coronavirus inhibitor, yet its underlying mechanism remained '
'largely unknown. Here, we found that non-structural protein 1 (Nsp1) of SARS-CoV-2 usurped '
'CsA-suppressed nuclear factor of activated T cells (NFAT) signaling to drive the expression '
'of cellular DEAD-box helicase 5 (DDX5), which facilitates viral replication. Nsp1 interacted '
'with calcineurin A (CnA) to displace the regulatory protein regulator of calcineurin 3 '
'(RCAN3) of CnA for NFAT activation. The influence of NFAT activation on SARS-CoV-2 '
'replication was also validated by using the Nsp1-deficient mutant virus. Calcineurin '
'inhibitors, such as CsA and VIVIT, inhibited SARS-CoV-2 replication and exhibited synergistic '
'antiviral effects when used in combination with nirmatrelvir. Our study delineated the '
'molecular mechanism of CsA-mediated inhibition of SARS-CoV-2 replication and the '
'anti-SARS-CoV-2 action of calcineurin inhibitors.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>IMPORTANCE</jats:title>\n'
' <jats:p>Cyclosporine A (CsA), commonly used to inhibit immune responses, is also '
'known to have anti-SARS-CoV-2 activity, but its mode of action remains elusive. Here, we '
'provide a model to explain how CsA antagonizes SARS-CoV-2 through three critical proteins: '
'DDX5, NFAT1, and Nsp1. DDX5 is a cellular facilitator of SARS-CoV-2 replication, and NFAT1 '
'controls the production of DDX5. Nsp1 is a viral protein absent from the mature viral '
'particle and capable of activating the function of NFAT1 and DDX5. CsA and similar agents '
'suppress Nsp1, NFAT1, and DDX5 to exert their anti-SARS-CoV-2 activity either alone or in '
'combination with Paxlovid.</jats:p>\n'
' </jats:sec>',
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'title': 'Nsp1 facilitates SARS-CoV-2 replication through calcineurin-NFAT signaling',
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'author': [ { 'given': 'Wai-Yin',
'family': 'Lui',
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{ 'given': 'Chon Phin',
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{ 'given': 'Pak-Hin Hinson',
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