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10.1073/pnas.2119467119 http://scihub22266oqcxt.onion/10.1073/pnas.2119467119 35363556!9169775!35363556     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2022 ; 119 (16): e2119467119 Nephropedia Template TP {{tp|p=35363556|t=2022. Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle |pdf=|usr=}}{{35363556}} gab.com Text Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=35363556 #FOAvip Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies due to structural and dynamic changes of the viral spike glycoprotein (S). The heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of S drive virus-host membrane fusion by assembly into a six-helix bundle, resulting in delivery of viral RNA into the host cell. We surveyed mutations of currently reported SARS-CoV-2 variants and selected eight mutations, including Q954H, N969K, and L981F from the Omicron variant, in the postfusion HR1HR2 bundle for functional and structural studies. We designed a molecular scaffold to determine cryogenic electron microscopy (cryo-EM) structures of HR1HR2 at 2.2-3.8 A resolution by linking the trimeric N termini of four HR1 fragments to four trimeric C termini of the Dps4 dodecamer from Nostoc punctiforme. This molecular scaffold enables efficient sample preparation and structure determination of the HR1HR2 bundle and its mutants by single-particle cryo-EM. Our structure of the wild-type HR1HR2 bundle resolves uncertainties in previously determined structures. The mutant structures reveal side-chain positions of the mutations and their primarily local effects on the interactions between HR1 and HR2. These mutations do not alter the global architecture of the postfusion HR1HR2 bundle, suggesting that the interfaces between HR1 and HR2 are good targets for developing antiviral inhibitors that should be efficacious against all known variants of SARS-CoV-2 to date. We also note that this work paves the way for similar studies in more distantly related viruses. Twit Text FOAVip Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=35363556 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35363556 #FOAvip English Wikipedia <ref>{{Cite pmid|35363556}}</ref> Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle #MMPMID35363556 Yang K; Wang C; White KI; Pfuetzner RA; Esquivies L; Brunger AT Proc Natl Acad Sci U S A 2022[Apr]; 119 (16): e2119467119 PMID35363556show ga Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies due to structural and dynamic changes of the viral spike glycoprotein (S). The heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of S drive virus-host membrane fusion by assembly into a six-helix bundle, resulting in delivery of viral RNA into the host cell. We surveyed mutations of currently reported SARS-CoV-2 variants and selected eight mutations, including Q954H, N969K, and L981F from the Omicron variant, in the postfusion HR1HR2 bundle for functional and structural studies. We designed a molecular scaffold to determine cryogenic electron microscopy (cryo-EM) structures of HR1HR2 at 2.2-3.8 A resolution by linking the trimeric N termini of four HR1 fragments to four trimeric C termini of the Dps4 dodecamer from Nostoc punctiforme. This molecular scaffold enables efficient sample preparation and structure determination of the HR1HR2 bundle and its mutants by single-particle cryo-EM. Our structure of the wild-type HR1HR2 bundle resolves uncertainties in previously determined structures. The mutant structures reveal side-chain positions of the mutations and their primarily local effects on the interactions between HR1 and HR2. These mutations do not alter the global architecture of the postfusion HR1HR2 bundle, suggesting that the interfaces between HR1 and HR2 are good targets for developing antiviral inhibitors that should be efficacious against all known variants of SARS-CoV-2 to date. We also note that this work paves the way for similar studies in more distantly related viruses. |*COVID-19[MESH] |*SARS-CoV-2/genetics[MESH] |*Spike Glycoprotein, Coronavirus/chemistry/genetics[MESH] |Conserved Sequence[MESH] |Humans[MESH] |Protein Domains[MESH]Structural conservation among variants of the SARS-CoV-2 spike postfus(epmc).pdf DeepDyve Pubget Overpricing