Open AccessStructural conservation among variants of the SARS-CoV-2 spike postfusion bundle
Author(s) -
Kailu Yang,
Chuchu Wang,
K. Ian White,
Richard A. Pfuetzner,
Luis Esquivies,
Axel T. Brunger
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119467119
Subject(s) - heptad repeat , biology , mutant , coronavirus , lipid bilayer fusion , virology , mutation , capsid , vero cell , biophysics , virus , genetics , peptide sequence , gene , covid-19 , disease , pathology , infectious disease (medical specialty) , medicine
Significance Emergence of viral pathogens necessitates new approaches to study viral fusion and entry into host cells. A key step in mediating fusion involves the formation of a six-helix bundle within the spike protein. Rapid structural characterization of this state has been difficult, hindering understanding of emerging variants. We developed a method to efficiently determine high-resolution bundle structures by molecular scaffolding and cryogenic electron microscopy. Using this method, we determined bundle structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. These structures reveal local effects of mutations on HR1HR2 interactions but global conservation of the bundle architecture among SARS-CoV-2 variants. We predict that inhibitors disrupting the postfusion bundle might be broadly efficacious against variants and even more distantly related lethal viruses.