High TiO 2 metadiabase dikes of the Hudson Highlands, New York and New Jersey; possible late Proterozoic rift rocks in the New York recess

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ID: 303211
1987
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Abstract

ABSTRACT

The ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair (Sb#15 and Sb#68) that can bind simultaneously to the SARS-CoV-2 spike-RBD and efficiently neutralize pseudotyped and live-viruses by interfering with ACE2 interaction. Two spatially-discrete epitopes identified by cryo-EM translated into the rational design of bispecific and tri-bispecific fusions constructs, exhibiting up to 100- and 1000-fold increase in neutralization potency. Cryo-EM of the sybody-spike complex further revealed a novel up-out RBD conformation. While resistant viruses emerged rapidly in the presence of single binders, no escape variants were observed in presence of the bispecific sybody. The multivalent bispecific constructs further increased the neutralization potency against globally-circulating SARS- CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the development of clinically relevant therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants.
Reference Key
openalex_W2316214065 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Nicholas M. Ratcliffe
Journal american journal of science
Year 1987
DOI
10.2475/ajs.287.8.817
URL
https://ajs.scholasticahq.com/article/60434.pdf
Keywords Keywords not found

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