Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected patients

Cantoni, Diego; Mayora-Neto, Martin; Thakur, Nazia; Elrefaey, Ahmed M.E.; Newman, Joseph; Vishwanath, Sneha; Nadesalingam, Angalee; Chan, Andrew; Smith, Peter J. S.; Castillo‐Olivares, Javier; Baxendale, Helen; Charleston, Bryan; Heeney, Jonathan L.; Bailey, Dalan; Temperton, Nigel

doi:10.1038/s42003-022-03325-9

Cited by 11 publications

(9 citation statements)

References 42 publications

(46 reference statements)

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“…As shown in Figure 1E , betaCov sequences form several clusters with the bat coronaviruses more dispersed. Some bat coronaviruses are projected close to SARS-CoV-2, Pangolin coronavirus, and RaTG13, a close relative of SARS-CoV-2 (Zhou et al, 2020) which can be neutralized by convalescent sera from COVID-19 patients (Cantoni et al, 2022). In a hypothetical bat virus sequence surveillance effort, a trajectory from point A to point B over time may indicate a series of mutations gradually leads to increased risk for infecting humans ( Figure 1E ).…”

Section: Resultsmentioning

confidence: 99%

wwLearning the language of proteins and predicting the impact of mutations

Hu,

Babinski,

Gibson

et al. 2024

Preprint

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Mutations in proteins directly impact their structure and function. Understanding the “language” of proteins, or the sequence to function (genotype-phenotype) relationship has many real-world applications. One set of applications includes those in biodefense, such as biological threat detection and biosurveillance, antibody engineering, and medical countermeasure development. In this study, we present a novel language model-based approach that can rapidly analyze vast collections of sequences, and make near real-time functional predictions that compare favorably to those made using conventional bioinformatic and experimental methods. Our findings reveal that tailored protein language models can predict protein mutation phenotypes, such as binding affinity or level of expression, when they are trained with high-throughput functional data. Protein language models applied to viral genomes can also discern the lineage within a family (e.g., sarbecovirus sequences). Coupled with sequenced-based biosurveillance, this type of model may provide early warning signals of potential zoonotic spillovers (i.e. host jumping) or “escape” from existing medical countermeasures posed by novel mutations. This research not only underscores the potential of ML and language models in addressing pressing challenges in understanding the mapping of sequence to function, but further elucidates their potential application in accelerating the response to biological threats as they evolve.

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Section: Resultsmentioning

confidence: 99%

wwLearning the language of proteins and predicting the impact of mutations

Hu,

Babinski,

Gibson

et al. 2024

Preprint

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“…Most recently, JN.1 has become the dominant strain globally 30 , harboring 58 total spike mutations with 27 of these in the RBD 29 . Impressively, the SARS-CoV-2 pandemic has now resulted in variants that are further evolved from the original Wuhan strain than other distinct coronaviruses such as RaTG13 32,33 ( Figure S1A ) which harbors only 26 amino acid differences from the Wuhan strain. Over the course of the pandemic, 131 differences in viral spike have arisen across variants of concern/interest, including several which occurred at the same position in the spike protein ( Figure S1B ).…”

Section: Resultsmentioning

confidence: 99%

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity

Roederer,

Cao,

St. Denis

et al. 2024

Preprint

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Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.

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“…It has previously been appreciated that COVID-19 vaccines can induce antibodies that at least partially neutralize selected animal sarbecoviruses 27,[62][63][64][65][66] . However, systematic analyses are lacking.…”

Section: Discussionmentioning

confidence: 99%

ACE2-independent sarbecovirus cell entry is supported by TMPRSS2-related enzymes and reduces sensitivity to antibody-mediated neutralization

Zhang,

Cheng,

Krüger

et al. 2024

Preprint

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The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract. In contrast, two bat sarbecovirus S proteins drove cell entry in an ACE2-independent, trypsin-dependent fashion and several ACE2-dependent S proteins could switch to the ACE2-independent entry pathway when exposed to trypsin. Several TMPRSS2-related cellular proteases but not the insertion of a multibasic cleavage site into the S protein allowed for ACE2-independent entry in the absence of trypsin and may support viral spread in the respiratory tract. Finally, the pan-sarbecovirus antibody S2H97 enhanced cell entry driven by two S proteins and this effect was reversed by trypsin. Similarly, plasma from quadruple vaccinated individuals neutralized entry driven by all S proteins studied, and use of the ACE2-independent, trypsin-dependent pathway reduced neutralization sensitivity. In sum, our study reports a pathway for entry into human cells that is ACE2-independent, supported by TMPRSS2-related proteases and associated with antibody evasion.

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Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected patients

Cited by 11 publications

References 42 publications

wwLearning the language of proteins and predicting the impact of mutations

wwLearning the language of proteins and predicting the impact of mutations

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity

ACE2-independent sarbecovirus cell entry is supported by TMPRSS2-related enzymes and reduces sensitivity to antibody-mediated neutralization

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