A key linear epitope for a potent neutralizing antibody to SARS-CoV-2 S-RBD

Li, Tingting; Han, Xiaojian; Wang, Ying‐Ming; Gu, Cheng; Wang, Jianwei; Hu, Chao; Li, Shenglong; Wang, Kai; Luo, Feiyang; Huang, Jingjing; Long, Yingyi; Song, Shuyi; Wang, Wang; Hu, Jie; Wu, Ruixue; Mu, Song; Hao, Yanan; Chen, Qian; Gao, Feng; Shen, Meiying; Long, Shunhua; Gong, Fang; Luo, Li; Wu, Yang; Xü, Wei; Cai, Xiujun; Qu, Di; Yuan, Zhenghong; Gao, Qi; Zhang, Guiji; He, Chaojun; Nai, Yaru; Deng, Kun; Du, Li; Tang, Ni; Xie, Youhua; Huang, Aiping; Jin, Aishun

doi:10.1101/2020.09.11.292631

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…Other investigators ( 81 ) using in vitro antibody selection identified a change at amino acid site S151 in the N-terminal domain, and we found mutations S151N and S151I in our patient samples. We also note that two variant amino acids (Gly446Val and Phe456Leu) that we identified were located in a linear epitope found to be critical for a neutralizing monoclonal antibody described recently by Li et al ( 82 ).…”

Section: Discussionsupporting

confidence: 70%

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

Long

Olsen

Christensen

et al. 2020

mBio

107

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We sequenced the genomes of 5,085 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains causing two coronavirus disease 2019 (COVID-19) disease waves in metropolitan Houston, TX, an ethnically diverse region with 7 million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston and from viruses recovered in an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotype and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein—the primary target of global vaccine efforts—are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR3022. Our report represents the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution. IMPORTANCE There is concern about second and subsequent waves of COVID-19 caused by the SARS-CoV-2 coronavirus occurring in communities globally that had an initial disease wave. Metropolitan Houston, TX, with a population of 7 million, is experiencing a massive second disease wave that began in late May 2020. To understand SARS-CoV-2 molecular population genomic architecture and evolution and the relationship between virus genotypes and patient features, we sequenced the genomes of 5,085 SARS-CoV-2 strains from these two waves. Our report provides the first molecular characterization of SARS-CoV-2 strains causing two distinct COVID-19 disease waves.

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Section: Discussionsupporting

confidence: 70%

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

Long

Olsen

Christensen

et al. 2020

mBio

107

View full text Add to dashboard Cite

show abstract

“…Other investigators (86) using in vitro antibody selection identified a change at amino acid site S151 in the N-terminal domain, and we found mutations S151N and S151I in our patient samples. We also note that two variant amino acids (Gly446Val and Phe456Leu) we identified are located in a linear epitope found to be critical for a neutralizing monoclonal antibody described recently by Li et al (87).…”

Section: Discussionsupporting

confidence: 69%

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

Long

Olsen

Christensen

et al. 2020

Preprint

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We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotypes and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein - the primary target of global vaccine efforts - are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR30022. Our study is the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves, and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.

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“…Experimental data pertaining to neutralization of S(G614) and S(D614) pseudoviruses have been reported in abundance. The majority of experiments demonstrate similar neutralization of both S(D614) and S(G614) PVs by antibodies or patient antisera directed against one or the other S protein variant [ 28 , 35 , 51 , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] ], while in some cases S(G614) exhibited greater susceptibility to neutralization [ 51 , 57 ]. Similar neutralization or greater susceptibility of the S(G614) variant have been reproduced with live SARS-CoV-2 as well [ 47 , 48 ].…”

Section: Introductionmentioning

confidence: 99%

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein

Jackson

Zhang

Farzan

et al. 2021

Biochemical and Biophysical Research Communications

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus which binds its cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters hosts cells through the action of its spike (S) glycoprotein displayed on the surface of the virion. Compared to the reference strain of SARS-CoV-2, the majority of currently circulating isolates possess an S protein variant characterized by an aspartic acid-to-glycine substitution at amino acid position 614 (D614G). Residue 614 lies outside the receptor binding domain (RBD) and the mutation does not alter the affinity of monomeric S protein for ACE2. However, S(G614), compared to S(D614), mediates more efficient ACE2-mediated transduction of cells by S-pseudotyped vectors and more efficient infection of cells and animals by live SARS-CoV-2. This review summarizes and synthesizes the epidemiological and functional observations of the D614G spike mutation, with focus on the biochemical and cell-biological impact of this mutation and its consequences for S protein function. We further discuss the significance of these recent findings in the context of the current global pandemic.

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A key linear epitope for a potent neutralizing antibody to SARS-CoV-2 S-RBD

Cited by 6 publications

References 26 publications

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein

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