Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain

Wang, Yanqun; Zhang, Zhaoyong; Yang, Minnan; Xiong, Xinyi; Yan, Qihong; Cao, Lei; Wei, Peilan; Zhang, Yuting; Zhang, Lu; Lv, Kexin; Chen, Jiantao; Liu, Xuesong; Zhao, Xiaochu; Xiao, Juxue; Zhang, Shengnan; Zhu, Airu; Gan, Mian; Zhang, Jingjun; Cai, Ruoxi; Zhuo, Jianfen; Zhang, Yanjun; Rao, Haiyue; Qu, Bin; Zhang, Yuanyuan; Chen, Lei; Dai, Jun; Cheng, Linling; Hu, Qingtao; Chen, Yaoqing; Lv, Huibin; So, Ray T.Y.; Peiris, Malik; Zhao, Jingxian; Liu, Xiaoqing; Mok, Chris Ka Pun; Wang, Xiangxi; Zhao, Jincun

doi:10.1016/j.celrep.2023.113653

Cited by 5 publications

(2 citation statements)

References 46 publications

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“…The antibody S309, which recognises a conserved epitope containing glycan, demonstrates strong neutralisation without competing with receptor attachment. Antibody cocktails including S309 enhance SARS-CoV-2 neutralisation, potentially limiting the emergence of escape mutants [185,186]. These findings highlight the therapeutic potential of these antibodies, especially S309, for prophylaxis or post-exposure therapy to mitigate severe COVID-19.…”

Section: Experimental Therapeutic Interventions Convalescent Plasma (...mentioning

confidence: 99%

“…These findings highlight the therapeutic potential of these antibodies, especially S309, for prophylaxis or post-exposure therapy to mitigate severe COVID-19. In addition, a study identified 11 potent neutralising antibodies against SARS-CoV-2, with antibody 414-1 showing the best IC50 of 1.75 nM, providing promising therapeutic candidates for COVID-19 treatment [185][186][187].…”

Section: Experimental Therapeutic Interventions Convalescent Plasma (...mentioning

confidence: 99%

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Unravelling Insights into the Evolution and Management of SARS-CoV-2

Mushebenge,

Ugbaja,

Mbatha

et al. 2024

BioMedInformatics

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Worldwide, the COVID-19 pandemic, caused by the brand-new coronavirus SARS-CoV-2, has claimed a sizable number of lives. The virus’ rapid spread and impact on every facet of human existence necessitate a continuous and dynamic examination of its biology and management. Despite this urgency, COVID-19 does not currently have any particular antiviral treatments. As a result, scientists are concentrating on repurposing existing antiviral medications or creating brand-new ones. This comprehensive review seeks to provide an in-depth exploration of our current understanding of SARS-CoV-2, starting with an analysis of its prevalence, pathology, and evolutionary trends. In doing so, the review aims to clarify the complex network of factors that have contributed to the varying case fatality rates observed in different geographic areas. In this work, we explore the complex world of SARS-CoV-2 mutations and their implications for vaccine efficacy and therapeutic interventions. The dynamic viral landscape of the pandemic poses a significant challenge, leading scientists to investigate the genetic foundations of the virus and the mechanisms underlying these genetic alterations. Numerous hypotheses have been proposed as the pandemic has developed, covering various subjects like the selection pressures driving mutation, the possibility of vaccine escape, and the consequences for clinical therapy. Furthermore, this review will shed light on current clinical trials investigating novel medicines and vaccine development, including the promising field of drug repurposing, providing a window into the changing field of treatment approaches. This study provides a comprehensive understanding of the virus by compiling the huge and evolving body of knowledge on SARS-CoV-2, highlighting its complexities and implications for public health, and igniting additional investigation into the control of this unprecedented global health disaster.

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Section: Experimental Therapeutic Interventions Convalescent Plasma (...mentioning

confidence: 99%

Section: Experimental Therapeutic Interventions Convalescent Plasma (...mentioning

confidence: 99%

Unravelling Insights into the Evolution and Management of SARS-CoV-2

Mushebenge,

Ugbaja,

Mbatha

et al. 2024

BioMedInformatics

View full text Add to dashboard Cite

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Defining the features and structure of neutralizing antibody targeting the silent face of the SARS‐CoV‐2 spike N‐terminal domain

Zhang,

Zhang

et al. 2024

MedComm

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Research on virus/receptor interactions has uncovered various mechanisms of antibody‐mediated neutralization against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, understanding of neutralization by antibodies targeting the silent face, which recognize epitopes on glycan shields, remains limited, and their potential protective efficacy in vivo is not well understood. This study describes a silent face neutralizing antibody, 3711, which targets a non‐supersite on the N‐terminal domain (NTD) of the spike protein. Cryo‐EM structure determination of the 3711 Fab in the spike complex reveals a novel neutralizing epitope shielded by glycans on the spike's silent face. Antibody 3711 inhibits the interaction between the receptor‐binding domain (RBD) and human angiotensin‐converting enzyme 2 (hACE2) through steric hindrance and exhibits superior in vivo protective effects compared to other reported NTD‐targeted monoclonal antibodies (mAbs). Competition assays and antibody repertoire analysis indicate the rarity of antibodies targeting the 3711‐related epitope in SARS‐CoV‐2 convalescents, suggesting the infrequency of NTD silent face‐targeted neutralizing antibodies during SARS‐CoV‐2 infection. As the first NTD silent face‐targeted neutralizing antibody against SARS‐CoV‐2, the identification of mAb 3711, with its novel neutralizing mechanism, enhances our understanding of neutralizing epitopes on glycan shields and elucidates epitope‐guided viral mutations that evade specific antibodies.

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Broadening sarbecovirus neutralization with bispecific antibodies combining distinct conserved targets on the receptor binding domain

Guerra,

Radić,

Brinkkemper

et al. 2024

Human Vaccines & Immunotherapeutics

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Monoclonal neutralizing antibodies (mAbs) are considered an important prophylactic against SARS-CoV-2 infection in at-risk populations and a strategy to counteract future sarbecovirus-induced disease. However, most mAbs isolated so far neutralize only a few sarbecovirus strains. Therefore, there is a growing interest in bispecific antibodies (bsAbs) which can simultaneously target different spike epitopes and thereby increase neutralizing breadth and prevent viral escape. Here, we generate and characterize a panel of 30 novel broadly reactive bsAbs using an efficient controlled Fab-arm exchange protocol. We specifically combine some of the broadest mAbs described so far, which target conserved epitopes on the receptor binding domain (RBD). Several bsAbs show superior cross-binding and neutralization compared to the parental mAbs and cocktails against sarbecoviruses from diverse clades, including recent SARS-CoV-2 variants. BsAbs which include mAb COVA2–02 are among the most potent and broad combinations. As a result, we study the unknown epitope of COVA2–02 and show that this mAb targets a distinct conserved region at the base of the RBD, which could be of interest when designing next-generation bsAb constructs to contribute to a better pandemic preparedness.

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Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain

Cited by 5 publications

References 46 publications

Unravelling Insights into the Evolution and Management of SARS-CoV-2

Unravelling Insights into the Evolution and Management of SARS-CoV-2

Defining the features and structure of neutralizing antibody targeting the silent face of the SARS‐CoV‐2 spike N‐terminal domain

Broadening sarbecovirus neutralization with bispecific antibodies combining distinct conserved targets on the receptor binding domain

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