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- W3117542466 abstract "The Spike (S)-protein of SARS-CoV-2 binds host-cell receptor ACE2 and requires proteolytic priming (S1/S2) and fusion-activation (S2) for viral entry. The S-protein furin-like motifs PRRAR685{downarrow} and KPSKR815{downarrow} indicated that proprotein convertases promote virus entry. We demonstrate that furin and PC5A induce cleavage at both sites, ACE2 enhances S2 processing, and their pharmacological inhibition (BOS-inhibitors) block endogenous cleavages. S1/S2-mutations (S1/S2) limit S-protein-mediated cell-to-cell fusion, similarly to BOS-inhibitors. Unexpectedly, TMPRSS2 does not cleave at S1/S2 or S2, but it can: (i) cleave/inactivate S-protein into S2a/S2b; (ii) shed ACE2; (iii) cleave S1-subunit into secreted S1, activities inhibited by Camostat. In lung-derived Calu-3 cells, BOS-inhibitors and {micro}S1/S2 severely curtail pH-independent viral entry, and BOS-inhibitors alone/with Camostat potently reduce infectious viral titer and cytopathic effects. Overall, our results show that: furin plays a critical role in generating fusion-competent S-protein, and indirectly, TMPRSS2 promotes viral entry, supporting furin and TMPRSS2 inhibitors as potential antivirals against SARS-CoV-2." @default.
- W3117542466 created "2021-01-05" @default.
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- W3117542466 date "2020-12-20" @default.
- W3117542466 modified "2023-09-27" @default.
- W3117542466 title "Furin cleaves SARS-CoV-2 spike-glycoprotein at S1/S2 and S2'for viral fusion/entry: indirect role for TMPRSS2" @default.
- W3117542466 cites W1517000857 @default.
- W3117542466 cites W1832976650 @default.
- W3117542466 cites W1965531501 @default.
- W3117542466 cites W1969168253 @default.
- W3117542466 cites W1974043792 @default.
- W3117542466 cites W1994915168 @default.
- W3117542466 cites W1998964868 @default.
- W3117542466 cites W2001675486 @default.
- W3117542466 cites W2010503769 @default.
- W3117542466 cites W2019469658 @default.
- W3117542466 cites W2022674779 @default.
- W3117542466 cites W2050446750 @default.
- W3117542466 cites W2064076043 @default.
- W3117542466 cites W2076863893 @default.
- W3117542466 cites W2086493164 @default.
- W3117542466 cites W2089025288 @default.
- W3117542466 cites W2094222285 @default.
- W3117542466 cites W2095807050 @default.
- W3117542466 cites W2101506295 @default.
- W3117542466 cites W2105149323 @default.
- W3117542466 cites W2126255146 @default.
- W3117542466 cites W2154497662 @default.
- W3117542466 cites W2209343511 @default.
- W3117542466 cites W223168254 @default.
- W3117542466 cites W2411708181 @default.
- W3117542466 cites W2470398908 @default.
- W3117542466 cites W2741332232 @default.
- W3117542466 cites W2777577494 @default.
- W3117542466 cites W2903899730 @default.
- W3117542466 cites W2965830542 @default.
- W3117542466 cites W2971662549 @default.
- W3117542466 cites W3005409321 @default.
- W3117542466 cites W3008876765 @default.
- W3117542466 cites W3009335299 @default.
- W3117542466 cites W3009906937 @default.
- W3117542466 cites W3009912996 @default.
- W3117542466 cites W3010441732 @default.
- W3117542466 cites W3011127849 @default.
- W3117542466 cites W3013093478 @default.
- W3117542466 cites W3013893137 @default.
- W3117542466 cites W3014067025 @default.
- W3117542466 cites W3014912119 @default.
- W3117542466 cites W3015438945 @default.
- W3117542466 cites W3016829967 @default.
- W3117542466 cites W3017302293 @default.
- W3117542466 cites W3017488348 @default.
- W3117542466 cites W3020667419 @default.
- W3117542466 cites W3020695284 @default.
- W3117542466 cites W3020838714 @default.
- W3117542466 cites W3022435472 @default.
- W3117542466 cites W3033543683 @default.
- W3117542466 cites W3035546072 @default.
- W3117542466 cites W3036597392 @default.
- W3117542466 cites W3036674128 @default.
- W3117542466 cites W3040035440 @default.
- W3117542466 cites W3042332408 @default.
- W3117542466 cites W3044321933 @default.
- W3117542466 cites W3044416430 @default.
- W3117542466 cites W3044702419 @default.
- W3117542466 cites W3048531412 @default.
- W3117542466 cites W3087347658 @default.
- W3117542466 cites W3089346069 @default.
- W3117542466 cites W3090108357 @default.
- W3117542466 cites W3090801115 @default.
- W3117542466 cites W3094419073 @default.
- W3117542466 cites W3094553382 @default.
- W3117542466 cites W3095988184 @default.
- W3117542466 cites W3102453076 @default.
- W3117542466 cites W3102688328 @default.
- W3117542466 cites W3105478020 @default.
- W3117542466 cites W3118947400 @default.
- W3117542466 cites W3121790907 @default.
- W3117542466 cites W3122083218 @default.
- W3117542466 cites W3122148095 @default.
- W3117542466 cites W3124805424 @default.
- W3117542466 cites W3128708221 @default.
- W3117542466 cites W3130156934 @default.