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10.1016/j.celrep.2022.111117

http://scihub22266oqcxt.onion/10.1016/j.celrep.2022.111117
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35839776!9250890!35839776
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suck abstract from ncbi


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pmid35839776      Cell+Rep 2022 ; 40 (3): 111117
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  • Amelioration of SARS-CoV-2 infection by ANO6 phospholipid scramblase inhibition #MMPMID35839776
  • Sim JR; Shin DH; Park PG; Park SH; Bae JY; Lee Y; Kang DY; Kim YJ; Aum S; Noh SH; Hwang SJ; Cha HR; Kim CB; Ko SH; Park S; Jeon D; Cho S; Lee GE; Kim J; Moon YH; Kim JO; Nam JS; Kim CH; Moon S; Chung YW; Park MS; Ryu JH; Namkung W; Lee JM; Lee MG
  • Cell Rep 2022[Jul]; 40 (3): 111117 PMID35839776show ga
  • As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca(2+) elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19).
  • |*COVID-19 Drug Treatment[MESH]
  • |Angiotensin-Converting Enzyme 2[MESH]
  • |Animals[MESH]
  • |Anoctamins[MESH]
  • |Humans[MESH]
  • |Mammals/metabolism[MESH]
  • |Phosphatidylserines[MESH]
  • |Phospholipid Transfer Proteins/metabolism[MESH]
  • |SARS-CoV-2[MESH]


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