Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD

Zhou, Yunjiao; Liu, Zezhong; Li, Shibo; Xü, Wei; Zhang, Qianqian; Silva, Israel Tojal da; Cheng, Li; Wu, Yanling; Jiang, Qingling; Liu, Zhenmi; Wang, Qiujing; Guo, Yu; Wu, Jianbo; Chengjian, Gu; Cai, Xiujun; Qu, Di; Mayer, Christian T.; Wang, Xiangxi; Jiang, Shibo; Ying, Tianlei; Yuan, Zhenghong; Xie, Youhua; Wen, Yumei; Lu, Lu; Wang, Qiao

doi:10.1016/j.celrep.2021.108699

Cited by 123 publications

(191 citation statements)

References 80 publications

(119 reference statements)

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“…Antibodies 2-43 and 2-51, together with XG006 and XG027 appeared to target epitopes obtained in the quaternary structure of S bridging RBD and NTD, and with the second set of NmAbs, 2-43, 2-51, XG006 and XG027 exhibit a steric hindrance-based inhibition. By neutralizing SARS-CoV-2 through NTD and/or RBD binding ( Liu L. et al, 2020 ; Zhou et al, 2021 ), 2-43, 2-51, XG006, and XG027 are good therapeutic targets. An in silico screening assay from 48A revealed that aside from binding to NTD, 4A8 binds to S1/S2 furin cleavage site ( Cheng et al, 2020 ), hampering the furin protease to access the site, which consequently inhibits a step toward the viral entry.…”

Section: Sars-cov-2 Nmab Molecular Neutralizing Activitiesmentioning

confidence: 99%

“…Besides the S1-specific hNmAbs, only five hNmAbs (0304-3H3, 6D3, 9A1, CM29, and XG012) showing to be specific to the SARS-CoV-2 S2 subunit have been reported ( Cheng et al, 2020 ; Chi et al, 2020b ; Voss et al, 2020 ; Zhou et al, 2021 ). 0304-3H3, exhibited the highest neutralizing capacity (IC 50 : 0.04 μg/ml) against the WT, but not the PT SARS-CoV-2, while 9A1 and CM29 exhibited very weak protection against SDARS-CoV-2 ( Chi et al, 2020b ; Voss et al, 2020 ).…”

Section: Sars-cov-2 Nmab Molecular Neutralizing Activitiesmentioning

confidence: 99%

“…Among the NmAbs tested for their cross-activity against other coronaviruses, XG014, 5F8, CC6.33, ACE2-Ig, mACE2-Ig, H014, and its related single domain antibody H014-Fab, EY6A, and aRBD-41 have been reported as showing a cross-binding to SARS-CoV, and all, but not 5F8 and aRBD-41 could potently cross-neutralize SARS-CoV ( Chi et al, 2020a ; Lei et al, 2020 ; Rogers et al, 2020 ; Zhou D. et al, 2020 ; Ma et al, 2021 ; Zhou et al, 2021 ). Interestingly, these NmAbs were demonstrated to recognize conserved residues between the RBDs of SARS-CoV and SARS-CoV-2.…”

Section: Sars-cov-2 Nmab Molecular Neutralizing Activitiesmentioning

confidence: 99%

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Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection

Kombe

Zahid

Mohammed

et al. 2021

Front. Mol. Biosci.

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The 2019–2020 winter was marked by the emergence of a new coronavirus (SARS-CoV-2) related disease (COVID-19), which started in Wuhan, China. Its high human-to-human transmission ability led to a worldwide spread within few weeks and has caused substantial human loss. Mechanical antiviral control approach, drug repositioning, and use of COVID-19 convalescent plasmas (CPs) were the first line strategies utilized to mitigate the viral spread, yet insufficient. The urgent need to contain this deadly pandemic has led searchers and pharmaceutical companies to develop vaccines. However, not all vaccines manufactured are safe. Besides, an alternative and effective treatment option for such an infectious disease would include pure anti-viral neutralizing monoclonal antibodies (NmAbs), which can block the virus at specific molecular targets from entering cells by inhibiting virus-cell structural complex formation, with more safety and efficiency than the CP. Indeed, there is a lot of molecular evidence about the protector effect and the use of molecular feature-based NmAbs as promising therapeutics to contain COVID-19. Thus, from the scientific publication database screening, we here retrieved antibody-related papers and summarized the repertory of characterized NmAbs against SARS-CoV-2, their molecular neutralization mechanisms, and their immunotherapeutic pros and cons. About 500 anti-SARS-CoV-2 NmAbs, characterized through competitive binding assays and neutralization efficacy, were reported at the writing time (January 2021). All NmAbs bind respectively to SARS-CoV-2 S and exhibit high molecular neutralizing effects against wild-type and/or pseudotyped virus. Overall, we defined six NmAb groups blocking SARS-CoV-2 through different molecular neutralization mechanisms, from which five potential neutralization sites on SARS-CoV-2 S protein are described. Therefore, more efforts are needed to develop NmAbs-based cocktails to mitigate COVID-19.

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Section: Sars-cov-2 Nmab Molecular Neutralizing Activitiesmentioning

confidence: 99%

Section: Sars-cov-2 Nmab Molecular Neutralizing Activitiesmentioning

confidence: 99%

Section: Sars-cov-2 Nmab Molecular Neutralizing Activitiesmentioning

confidence: 99%

See 1 more Smart Citation

Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection

Kombe

Zahid

Mohammed

et al. 2021

Front. Mol. Biosci.

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show abstract

“…Anti-S antibody levels correlate well with those of neutralizing antibodies, including anti-RBD [30,33,38,48,62,64,81,86,88,90,106,[126][127][128][129][130][131][132]. Piccoli et al [50] have proposed that some 90% of neutralizing activity is due to anti-RBD antibody, and they have particularly mapped two dominant subepitopes.…”

Section: Correlations With Immunity or Protectionmentioning

confidence: 98%

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Cimolai¹

2021

CHI

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In the absence of effective antiviral chemotherapy and still in the context of emerging vaccines for severe acute respiratory syndrome-CoV-2 infections, passive immunotherapy remains a key treatment and possible prevention strategy. What might initially be conceived as a simplified donor-recipient process, the intricacies of donor plasma, IV immunoglobulins, and monoclonal antibody modality applications are becoming more apparent. Key targets of such treatment have largely focused on virus neutralization and the specific viral components of the attachment Spike protein and its constituents (e.g., receptor binding domain, N-terminal domain). The cumulative laboratory and clinical experience suggests that beneficial protective and treatment outcomes are possible. Both a dose-and a time-dependency emerge. Lesser understood are the concepts of bioavailability and distribution. Apart from direct antigen binding from protective immunoglobulins, antibody effector functions have potential roles in outcome. In attempting to mimic the natural but variable response to infection or vaccination, a strong functional polyclonal approach attracts the potential benefits of attacking antigen diversity, high antibody avidity, antibody persistence, and protection against escape viral mutation. The availability and ease of administration for any passive immunotherapy product must be considered in the current climate of need. There is never a perfect product, but yet there is considerable room for improving patient outcomes. Given the variability of human genetics, immunity, and disease, and given the nuances of the virus and its potential for change, passive immunotherapy can be developed that will be effective for some but not all patients. An understanding of such patient variability and limitations is just as important as the understanding of the direct interactions between immunotherapy and virus.

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“…Some patients dying from the infection had both high viral loads and antibody titers, indicating these antibodies were unable to neutralize the virus. The in vitro correlates of ADE are only partially understood [ 28 ].…”

Section: The Immune Response To Sars-cov-2mentioning

confidence: 99%

Perspective: the nose and the stomach play a critical role in the NZACE2-Pātari* (modified ACE2) drug treatment project of SARS-CoV-2 infection

Ameratunga

Woon

Steele

et al. 2021

Expert Review of Clinical Immunology

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Background: COVID-19 has caused calamitous health, economic and societal consequences globally. Currently, there is no effective treatment for the infection. Areas covered: We have recently described the NZACE2-Pātari project, which seeks to administer modified Angiotensin Converting Enzyme 2 (ACE2) molecules early in the infection to intercept and block SARS-CoV-2 binding to the pulmonary epithelium. Expert opinion: Since the nasopharyngeal mucosa is infected in the first asymptomatic phase of the infection, treatment of the nose is likely to be safe and potentially effective. The intercepted virus will be swallowed and destroyed in the stomach. There is however a limited window of opportunity to alter the trajectory of the infection in an individual patient, which requires access to rapid testing for SARS-CoV-2. The proposed strategy is analogous to passive immunization of viral infections such as measles and may be of particular benefit to immunodeficient and unvaccinated individuals.

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Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD

Cited by 123 publications

References 80 publications

Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection

Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Perspective: the nose and the stomach play a critical role in the NZACE2-Pātari* (modified ACE2) drug treatment project of SARS-CoV-2 infection

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