8sk5
From Proteopedia
Crystal structure of the SARS-CoV-2 neutralizing VHH 7A9 bound to the spike receptor binding domain
Structural highlights
Publication Abstract from PubMedCoronaviruses have been the causative agent of three epidemics and pandemics in the past two decades, including the ongoing COVID-19 pandemic. A broadly-neutralizing coronavirus therapeutic is desirable not only to prevent and treat COVID-19, but also to provide protection for high-risk populations against future emergent coronaviruses. As all coronaviruses use spike proteins on the viral surface to enter the host cells, and these spike proteins share sequence and structural homology, we set out to discover cross-reactive biologic agents targeting the spike protein to block viral entry. Through llama immunization campaigns, we have identified single domain antibodies (VHHs) that are cross-reactive against multiple emergent coronaviruses (SARS-CoV, SARS-CoV-2, and MERS). Importantly, a number of these antibodies show sub-nanomolar potency towards all SARS-like viruses including emergent CoV-2 variants. We identified nine distinct epitopes on the spike protein targeted by these VHHs. Further, by engineering VHHs targeting distinct, conserved epitopes into multi-valent formats, we significantly enhanced their neutralization potencies compared to the corresponding VHH cocktails. We believe this approach is ideally suited to address both emerging SARS-CoV-2 variants during the current pandemic as well as potential future pandemics caused by SARS-like coronaviruses. Discovery and multimerization of cross-reactive single-domain antibodies against SARS-like viruses to enhance potency and address emerging SARS-CoV-2 variants.,Hollingsworth SA, Noland CL, Vroom K, Saha A, Sam M, Gao Q, Zhou H, Grandy DU, Singh S, Wen Z, Warren C, Ma XS, Malashock D, Galli J, Go G, Eddins M, Mayhood T, Sathiyamoorthy K, Fridman A, Raoufi F, Gomez-Llorente Y, Patridge A, Tang Y, Chen SJ, Bailly M, Ji C, Kingsley LJ, Cheng AC, Geierstanger BH, Gorman DM, Zhang L, Pande K Sci Rep. 2023 Aug 22;13(1):13668. doi: 10.1038/s41598-023-40919-7. PMID:37608223[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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