Detection of antibodies neutralizing historical and emerging SARS-CoV-2 strains using a thermodynamically coupled de novo biosensor system

Zhang, Jason Z.; Yeh, Hsien‐Wei; Walls, Alexandra C.; Wicky, Basile I. M.; Sprouse, Kaiti; VanBlargan, Laura A.; Treger, Rebecca S.; Quijano‐Rubio, Alfredo; Pham, Minh N.; Kraft, John C.; Haydon, Ian C; Yang, Wei; DeWitt, Michelle; Chow, Cameron M.; Carter, Lauren; Wener, Mark H.; Stewart, Lance; Veesler, David; Diamond, Michael S.; Baker, David

doi:10.1101/2021.06.22.449355

Cited by 1 publication

(1 citation statement)

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“…Although this approach does not quantify the effect of RBD mutations on mAb neutralization, it has proved useful as a screening assay to identify mutations that require further study in cell culture. High-throughput biochemical assays such as enzyme-linked immunosorbent assays (ELISAs) are also being developed to allow clinical laboratories to measure the ability of plasma to inhibit ACE2 binding to RBDs belonging to different SARS-CoV-2 variants [132][133][134] .…”

Section: In Vitro Selection and Neutralization Experimentsmentioning

confidence: 99%

The biological and clinical significance of emerging SARS-CoV-2 variants

et al. 2021

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Among the many unprecedented aspects of the SARS-CoV-2 pandemic is the intense virological monitoring that has occurred, with more than two million virus isolates having undergone partial or complete genomic sequencing. Initially, genetic sequencing suggested that SARS-CoV-2 was exceptionally well adapted to humans, spreading rapidly with little evidence for natural selection among circulating viruses. This changed during the later months of 2020, with the first reports of emergent SARS-CoV-2 variants associated with increased transmissibility, disease severity and escape from humoral immunity.In this Review, we create a framework for understanding SARS-COV-2 variants by describing fundamental aspects of SARS-CoV-2 evolution, the structure and function of the SARS-CoV-2 spike protein and the laboratory methods used to characterize spike variants. We then describe the biological properties and epidemiological characteristics of these variants and their associated mutations. Lastly, we describe the types of study required for the research, clinical and public health communities to respond to the new threat posed by emerging SARS-CoV-2 variants. Given the wide public interest in this topic, we provide a box of key points. We also provide a repository of the SARS-CoV-2 variant neutralization data discussed in this Review (Stanford University Coronavirus Antiviral & Resistance Database -Susceptibility Data). SARS-CoV-2 evolutionCoronaviruses contain an exonuclease enzyme that reduces their replication error rate by about 15-fold to 20-fold in vitro, resulting in an in vivo viral mutation rate about 10-fold lower than that of influenza 1-3 . Nonetheless, they accumulate mutations and generate further diversity through the process of recombination when variants with different mutations infect the same host [4][5][6] . Recombination between different SARS-related coronaviruses is likely to have led to the emergence of SARS-CoV-2 (ref. 7 ) and, although it can be difficult to detect owing to the similarity of most sequences, recombination is occurring to some extent among circulating SARS-CoV-2 variants 6,8 . Additionally, host-mediated RNA editing by APOBeC and ADAr enzymes, as evidenced by the dominance of C to U changes in specific dinucleotide contexts, contributes to SARS-CoV-2 diversity 9,10 .Although it had been previously assumed that waning immunity explained the observation that people are commonly reinfected with endemic common-cold coronaviruses 11 , recent studies suggest that antigenic drift also contributes to the lack of long-lasting protection following coronavirus infections 12,13 . HCoV-229E and HCoV-OC43 sequences over a 30-year period demonstrate a ladder-like phylogenetic tree topology consistent with the emergence of novel variants sweeping

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Section: In Vitro Selection and Neutralization Experimentsmentioning

confidence: 99%