Matches in SemOpenAlex for { <https://semopenalex.org/work/W3126273453> ?p ?o ?g. }
- W3126273453 abstract "SUMMARY The newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. Screening a SARS-CoV-2 expression library identified ORF7b and ORF8 that suppressed IFN induction via inducing the deamidation of interferon regulatory factor 3 (IRF3). Deamidated IRF3 fails to bind the promoters of classic IRF3-responsible genes, thus muting IFN induction. Conversely, a shRNA-mediated screen focused on cellular glutamine amidotransferases corroborated that CTPS1 deamidates IRF3 to inhibit IFN induction. Functionally, ORF7b and ORF8 activate CTPS1 to promote de novo CTP synthesis while shutting down IFN induction. De novo synthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation." @default.
- W3126273453 created "2021-02-15" @default.
- W3126273453 creator A5007989189 @default.
- W3126273453 creator A5020643827 @default.
- W3126273453 creator A5025300076 @default.
- W3126273453 creator A5025988358 @default.
- W3126273453 creator A5033913214 @default.
- W3126273453 creator A5042895806 @default.
- W3126273453 creator A5053814912 @default.
- W3126273453 creator A5059083216 @default.
- W3126273453 creator A5062116814 @default.
- W3126273453 creator A5062907814 @default.
- W3126273453 creator A5066474998 @default.
- W3126273453 creator A5068164225 @default.
- W3126273453 creator A5074197755 @default.
- W3126273453 creator A5074770517 @default.
- W3126273453 creator A5085217990 @default.
- W3126273453 creator A5087570147 @default.
- W3126273453 date "2021-02-07" @default.
- W3126273453 modified "2023-10-01" @default.
- W3126273453 title "Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection" @default.
- W3126273453 cites W1216912431 @default.
- W3126273453 cites W1585380514 @default.
- W3126273453 cites W2000177767 @default.
- W3126273453 cites W2019737732 @default.
- W3126273453 cites W2039910403 @default.
- W3126273453 cites W2042433863 @default.
- W3126273453 cites W2044621879 @default.
- W3126273453 cites W2065821845 @default.
- W3126273453 cites W2078154360 @default.
- W3126273453 cites W2087799531 @default.
- W3126273453 cites W2098188064 @default.
- W3126273453 cites W2106248075 @default.
- W3126273453 cites W2146228523 @default.
- W3126273453 cites W2169933147 @default.
- W3126273453 cites W2338827139 @default.
- W3126273453 cites W2549958644 @default.
- W3126273453 cites W2601590724 @default.
- W3126273453 cites W2616485542 @default.
- W3126273453 cites W2794109144 @default.
- W3126273453 cites W2885484032 @default.
- W3126273453 cites W2896767268 @default.
- W3126273453 cites W2919569133 @default.
- W3126273453 cites W2938629106 @default.
- W3126273453 cites W2954760406 @default.
- W3126273453 cites W2963402728 @default.
- W3126273453 cites W2973917566 @default.
- W3126273453 cites W2979457612 @default.
- W3126273453 cites W3004280078 @default.
- W3126273453 cites W3009912996 @default.
- W3126273453 cites W3016467573 @default.
- W3126273453 cites W3016910743 @default.
- W3126273453 cites W3018023298 @default.
- W3126273453 cites W3020644521 @default.
- W3126273453 cites W3021577619 @default.
- W3126273453 cites W3022285953 @default.
- W3126273453 cites W3027231799 @default.
- W3126273453 cites W3027630905 @default.
- W3126273453 cites W3028036282 @default.
- W3126273453 cites W3030537287 @default.
- W3126273453 cites W3032677067 @default.
- W3126273453 cites W3036339225 @default.
- W3126273453 cites W3036912690 @default.
- W3126273453 cites W3039377995 @default.
- W3126273453 cites W3041667892 @default.
- W3126273453 cites W3041968020 @default.
- W3126273453 cites W3045552416 @default.
- W3126273453 cites W3045802278 @default.
- W3126273453 cites W3063771132 @default.
- W3126273453 cites W3087744389 @default.
- W3126273453 cites W3087924281 @default.
- W3126273453 cites W3091814234 @default.
- W3126273453 cites W3092136311 @default.
- W3126273453 cites W3093061534 @default.
- W3126273453 cites W3095926067 @default.
- W3126273453 cites W3099070704 @default.
- W3126273453 cites W3122243405 @default.
- W3126273453 doi "https://doi.org/10.1101/2021.02.05.429959" @default.
- W3126273453 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7872357" @default.
- W3126273453 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33564769" @default.
- W3126273453 hasPublicationYear "2021" @default.
- W3126273453 type Work @default.
- W3126273453 sameAs 3126273453 @default.
- W3126273453 citedByCount "8" @default.
- W3126273453 countsByYear W31262734532021 @default.
- W3126273453 countsByYear W31262734532022 @default.
- W3126273453 countsByYear W31262734532023 @default.
- W3126273453 crossrefType "posted-content" @default.
- W3126273453 hasAuthorship W3126273453A5007989189 @default.
- W3126273453 hasAuthorship W3126273453A5020643827 @default.
- W3126273453 hasAuthorship W3126273453A5025300076 @default.
- W3126273453 hasAuthorship W3126273453A5025988358 @default.
- W3126273453 hasAuthorship W3126273453A5033913214 @default.
- W3126273453 hasAuthorship W3126273453A5042895806 @default.
- W3126273453 hasAuthorship W3126273453A5053814912 @default.
- W3126273453 hasAuthorship W3126273453A5059083216 @default.
- W3126273453 hasAuthorship W3126273453A5062116814 @default.
- W3126273453 hasAuthorship W3126273453A5062907814 @default.
- W3126273453 hasAuthorship W3126273453A5066474998 @default.
- W3126273453 hasAuthorship W3126273453A5068164225 @default.