Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2

Sun, Xiaoyu; Yi, Chunyan; Zhu, Yuanfei; Ding, Longfei; Xia, Shuai; Chen, Xingchen; Mu, Lan; Gu, Cheng; Lü, Xiao; Fu, Yadong; Chen, Shuangfeng; Zhang, Tianlong; Zhang, Yaguang; Yang, Zhuo; Ma, Liyan; Gu, Wangpeng; Hu, Gaowei; Du, Shujuan; Yan, Renhong; Fu, Weihui; Yuan, Songhua; Qiu, Chenli; Zhao, Chen; Zhang, Xiaoyan; He, Yonghui; Qu, Aidong; Xu, Zhou; Li, Xiuling; Wong, Gary; Deng, Qiang; Zhou, Qiang; Lu, Hongzhou; Ling, Zhiyang; Ding, Jianping; Lu, Lu; Xu, Jianqing; Xie, Youhua; Sun, Bing

doi:10.1038/s41564-022-01155-3

Cited by 75 publications

(104 citation statements)

References 53 publications

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“…Apart from the SH region mentioned earlier, S2 FPs are also highly conserved among all coronavirus genera, suggesting that broad-spectrum antibodies could be found by targeting this epitope 86 – 88 . Some recently identified antibodies to this epitope have excellent broadly neutralizing activity against alpha-CoVs, beta-CoVs and even some gamma-CoVs and delta-CoVs 86 , 87 .…”

Section: The S2 Fpsmentioning

confidence: 80%

“…Combining two or more bnAbs targeting different epitopes as therapeutics (for example, different RBD class antibodies) or combining RBD-targeting antibodies with NTD-targeting and/or S2-targeting antibodies might be a feasible strategy against COVID-19. Some antibody cocktails, such as S2E12 and C77G12, 76E1 and CB6, and COV2-2196 and COV2-2130, have already been explored 54 , 87 , 88 , but more combinations need to be tested in clinical trials. Furthermore, some ACE2-targeting antibodies have been reported to confer protection in animal models against infection by SARS-CoV-2 and other SARS-like coronaviruses by competing with the S protein for receptor binding 101 , 102 , and these antibodies could be used in combination with the S protein-targeting antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, 76E1 (Fig. 2d ) was identified as another S2 FP-targeting nAb that shows extraordinary neutralizing breadth, including for alpha-CoVs, beta-CoVs and a few gamma-CoVs and delta-CoVs 88 . It has been proved that 76E1 can potently neutralize SARS-CoV-2 both in vitro and in vivo 88 .…”

Section: The S2 Fpsmentioning

confidence: 99%

“…2d ) was identified as another S2 FP-targeting nAb that shows extraordinary neutralizing breadth, including for alpha-CoVs, beta-CoVs and a few gamma-CoVs and delta-CoVs 88 . It has been proved that 76E1 can potently neutralize SARS-CoV-2 both in vitro and in vivo 88 . Like C77G12, a synergistic effect of 76E1 can be observed when the S protein contacts some RBD-targeting nAbs as well as ACE2 (ref.…”

Section: The S2 Fpsmentioning

confidence: 99%

“…Like C77G12, a synergistic effect of 76E1 can be observed when the S protein contacts some RBD-targeting nAbs as well as ACE2 (ref. 88 ). Taken together, these findings show that S2-directed antibodies target prominently conserved epitopes and exhibit the broadest neutralizing spectrum to date.…”

Section: The S2 Fpsmentioning

confidence: 99%

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Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged pathogenic human coronavirus that belongs to the sarbecovirus lineage of the genus Betacoronavirus. The ancestor strain has evolved into a number of variants of concern, with the Omicron variant of concern now having many distinct sublineages. The ongoing COVID-19 pandemic caused by SARS-CoV-2 has caused serious damage to public health and the global economy, and one strategy to combat COVID-19 has been the development of broadly neutralizing antibodies for prophylactic and therapeutic use. Many are in preclinical and clinical development, and a few have been approved for emergency use. Here we summarize neutralizing antibodies that target four key regions within the SARS-CoV-2 spike (S) protein, namely the N-terminal domain and the receptor-binding domain in the S1 subunit, and the stem helix region and the fusion peptide region in the S2 subunit. Understanding the characteristics of these broadly neutralizing antibodies will accelerate the development of new antibody therapeutics and provide guidance for the rational design of next-generation vaccines.

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Section: The S2 Fpsmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: The S2 Fpsmentioning

confidence: 99%

Section: The S2 Fpsmentioning

confidence: 99%

Section: The S2 Fpsmentioning

confidence: 99%

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Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

et al. 2022

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Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers

Liu,

Lu,

Chen

et al. 2023

BioFactors

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Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high‐throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid‐phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide‐based therapeutics and diagnostic tools for various biomedical challenges.

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Pan‐coronavirus fusion inhibitors to combat COVID‐19 and other emerging coronavirus infectious diseases

Lan

Wang

Jiao

et al. 2022

Journal of Medical Virology

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative agent of the currently ongoing coronavirus disease 2019 (COVID‐19) pandemic, has posed a serious threat to global public health. Recently, several SARS‐CoV‐2 variants of concern (VOCs) have emerged and caused numerous cases of reinfection in convalescent COVID‐19 patients, as well as breakthrough infections in vaccinated individuals. This calls for the development of broad‐spectrum antiviral drugs to combat SARS‐CoV‐2 and its VOCs. Pan‐coronavirus fusion inhibitors, targeting the conserved heptad repeat 1 (HR1) in spike protein S2 subunit, can broadly and potently inhibit infection of SARS‐CoV‐2 and its variants, as well as other human coronaviruses. In this review, we summarized the most recent development of pan‐coronavirus fusion inhibitors, such as EK1, EK1C4, and EKL1C, and highlighted their potential application in combating current COVID‐19 infection and reinfection, as well as future emerging coronavirus infectious diseases.

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Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2

Cited by 75 publications

References 53 publications

Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers

Pan‐coronavirus fusion inhibitors to combat COVID‐19 and other emerging coronavirus infectious diseases

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