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10.1101/2020.08.08.238469 http://scihub22266oqcxt.onion/10.1101/2020.08.08.238469 32817938!7430568!32817938     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\32817938.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       bioRxiv 2020 ; ä (ä): ä Nephropedia Template TP {{tp|p=32817938|t=2020. An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation |pdf=|usr=}}{{32817938}} gab.com Text An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation JO: bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=32817938 #FOAvip Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. By screening a yeast surface-displayed library of synthetic nanobody sequences, we identified a panel of nanobodies that bind to multiple epitopes on Spike and block ACE2 interaction via two distinct mechanisms. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for SARS-CoV-2 Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains stability and function after aerosolization, lyophilization, and heat treatment. These properties may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century. Twit Text FOAVip An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation ????bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=32817938 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32817938 #FOAvip English Wikipedia <ref>{{Cite pmid|32817938}}</ref> An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation #MMPMID32817938 Schoof M; Faust B; Saunders RA; Sangwan S; Rezelj V; Hoppe N; Boone M; Billesbolle CB; Puchades C; Azumaya CM; Kratochvil HT; Zimanyi M; Deshpande I; Liang J; Dickinson S; Nguyen HC; Chio CM; Merz GE; Thompson MC; Diwanji D; Schaefer K; Anand AA; Dobzinski N; Zha BS; Simoneau CR; Leon K; White KM; Chio US; Gupta M; Jin M; Li F; Liu Y; Zhang K; Bulkley D; Sun M; Smith AM; Rizo AN; Moss F; Brilot AF; Pourmal S; Trenker R; Pospiech T; Gupta S; Barsi-Rhyne B; Belyy V; Barile-Hill AW; Nock S; Liu Y; Krogan NJ; Ralston CY; Swaney DL; Garcia-Sastre A; Ott M; Vignuzzi M; Walter P; Manglik A bioRxiv 2020[Aug]; ä (ä): ä PMID32817938show ga Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. By screening a yeast surface-displayed library of synthetic nanobody sequences, we identified a panel of nanobodies that bind to multiple epitopes on Spike and block ACE2 interaction via two distinct mechanisms. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for SARS-CoV-2 Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains stability and function after aerosolization, lyophilization, and heat treatment. These properties may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century. äAn ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking S(epmc).pdf DeepDyve Pubget Overpricing