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10.1016/j.isci.2022.104311

http://scihub22266oqcxt.onion/10.1016/j.isci.2022.104311
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35502318!9044693!35502318
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suck abstract from ncbi


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pmid35502318      iScience 2022 ; 25 (5): 104311
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  • Synthetic lethality-based prediction of anti-SARS-CoV-2 targets #MMPMID35502318
  • Pal LR; Cheng K; Nair NU; Martin-Sancho L; Sinha S; Pu Y; Riva L; Yin X; Schischlik F; Lee JS; Chanda SK; Ruppin E
  • iScience 2022[May]; 25 (5): 104311 PMID35502318show ga
  • Novel strategies are needed to identify drug targets and treatments for the COVID-19 pandemic. The altered gene expression of virus-infected host cells provides an opportunity to specifically inhibit viral propagation via targeting the synthetic lethal and synthetic dosage lethal (SL/SDL) partners of such altered host genes. Pursuing this disparate antiviral strategy, here we comprehensively analyzed multiple in vitro and in vivo bulk and single-cell RNA-sequencing datasets of SARS-CoV-2 infection to predict clinically relevant candidate antiviral targets that are SL/SDL with altered host genes. The predicted SL/SDL-based targets are highly enriched for infected cell inhibiting genes reported in four SARS-CoV-2 CRISPR-Cas9 genome-wide genetic screens. We further selected a focused subset of 26 genes that we experimentally tested in a targeted siRNA screen using human Caco-2 cells. Notably, as predicted, knocking down these targets reduced viral replication and cell viability only under the infected condition without harming noninfected healthy cells.
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