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Message: <blockquote data-quote="imhotep" data-source="post: 26653204" data-attributes="member: 562115">A recently published paper states that -"Current COVID-19 vaccines and many clinical diagnostics are based on the structure and function of the SARS-CoV-2 spike ectodomain. Using hydrogen deuterium exchange mass spectrometry, we have uncovered that, in addition to the prefusion structure determined by cryo-EM, this protein adopts an alternative conformation that interconverts slowly with the canonical prefusion structure. This new conformation—an open trimer— contains easily accessible RBDs. It exposes the conserved trimer interface buried in the prefusion conformation, thus exposing potential epitopes for pan-coronavirus antibody and ligand recognition....."The above abstract doesn't provide much useful information to many....but,Just in brief, a team from the University of California in Berkeley, the University of Texas at Austin, and Chan Zuckerberg Biohub in San Francisco have identified a new conformation exposing the conserved trimer interface that is otherwise buried in the prefusion state. This will lead to the opening up of potential new therapeutic targets.Many would be aware that the Covid-19 Spike is a large trimeric protein that uses it's receptor-binding domain (RBD) to attach with the host cell ACE2 receptor. A stabilized version of the Spike ectodomain S2-P was widely used to develop the vaccines. Ectodomain usually refers to parts of proteins that make contact with surfaces - only after the attachment the entry into the host cell takes place. There are custom Protein Data Libraries where you can get these structures.The RBDs have "up" & "down" conformations with the "up" allowing the ACE2 binding. After the binding and cleavage the Spike refolds allowing for prefusion, and subsequent post-fusion.This team of researchers found that the spike protein populates two conformations within the prefusion state – with one particular state identified, will help to improve the development of diagnostics, therapeutics, and vaccines.This state exposes broadly neutralization-sensitive epitopes that are in the most highly conserved part of the Spike – the S2 trimer interface – and therefore present an ideal target for vaccines that would provide protection across different coronaviruses.PS: Let's hope someone will find a breakthrough that will lead to a drug or a vaccine that'll cover any variant of the coronavirus.</blockquote>

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