SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface

Bertoglio, Federico; Meier, Doris; Langreder, Nora; Steinke, Stephan; Rand, Ulfert; Simonelli, Luca; Heine, Philip Alexander; Ballmann, Rico; Schneider, Kai-Thomas; Roth, Kristian Daniel Ralph; Ruschig, Maximilian; Riese, Peggy; Eschke, Kathrin; Kim, Yeonsu; Schäckermann, Dorina; Pedotti, Mattia; Kühn, Philipp; Zock-Emmenthal, Susanne; Wöhrle, Johannes; Kilb, Normann; Herz, Tobias; Becker, Marlies; Grasshoff, Martina; Wenzel, Esther Veronika; Russo, Giulio; Kröger, Andrea; Brunotte, Linda; Ludwig, Stephan; Fühner, Viola; Krämer, Stefan; Dübel, Stefan; Varani, Luca; Roth, Günter; Čičin‐Šain, Luka; Schubert, Maren; Hust, Michael

doi:10.1038/s41467-021-21609-2

Cited by 74 publications

(53 citation statements)

References 85 publications

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“…Moreover, they confirmed that these mAbs were not SARS-CoV-specific antibodies after isolating other panels of antibodies reacting with SARS-CoV-2 from three healthy adult donors with serological evidence of circulating HCoV exposure and no history of SARS-CoV or SARS-CoV-2 infection. Secondly, Bertoglio et al ( Bertoglio et al, 2020 ) also isolated 17 proven SARS-CoV-2-specific NmAbs with high protective efficacy against WT infection from pre-pandemic healthy donors ( Table 2 ). All the 17 NmAbs recognize isolated RBD, and most of them, but not all, overlap the ACE2 binding site on SARS-CoV-2 S1, and as they exhibit a synergic neutralization effect, they revealed not to target the same epitopes on RBD.…”

Section: Sars-cov-2 Nmab Molecular Neutralizing Activitiesmentioning

confidence: 99%

“…sarbecoviruses are a subgenus of β-coronaviruses that contain SARS-CoV, SARS-CoV-2, and other circulating HCoVs. Studies on the isolation of NmAbs against SARS-CoV-2 have revealed the existence of conserved neutralization sites in sarbecoviruses capable of being reached by cross-neutralizing antibodies ( Bertoglio et al, 2020 ; Wec et al, 2020 ). This is very beneficial as it suggests that the use of broad sarbecovirus neutralizing antibodies as an immunotherapeutic cocktail would be an option to help mitigate not only COVID-19 but also other HCoVs associated diseases, as well as preventing the emergence of other sarbecovirus mutants.…”

Section: Advantages Of Anti-sars-cov-2 Nmabsmentioning

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: Advantages Of Anti-sars-cov-2 Nmabsmentioning

confidence: 99%

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

Kombe

Zahid

Mohammed

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

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“…Phage display has been one of the most powerful drug discovery technologies to lead to the development of FDA-approved peptide and antibody drugs for various diseases (e.g., hereditary angioedema, immune thrombocytopenic purpura, rheumatoid arthritis, and uveitis) [33,45,206] The success of phage display-derived drug molecules as well as the growing interest in peptides/antibodies in the biopharmaceutical market make phage display technology a popular approach for antiviral discovery. In fact, since the beginning of the latest coronavirus outbreak, several research groups have screened phage libraries to develop neutralizing recombinant antibodies against SARS-CoV-2 [83,191,[207][208][209][210][211][212].…”

Section: Perspectivementioning

confidence: 99%

Discovery of Antivirals Using Phage Display

Sokullu

Gauthier

Coulombe

2021

Viruses

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The latest coronavirus disease outbreak, COVID-19, has brought attention to viral infections which have posed serious health threats to humankind throughout history. The rapid global spread of COVID-19 is attributed to the increased human mobility of today’s world, yet the threat of viral infections to global public health is expected to increase continuously in part due to increasing human–animal interface. Development of antiviral agents is crucial to combat both existing and novel viral infections. Recently, there is a growing interest in peptide/protein-based drug molecules. Antibodies are becoming especially predominant in the drug market. Indeed, in a remarkably short period, four antibody therapeutics were authorized for emergency use in COVID-19 treatment in the US, Russia, and India as of November 2020. Phage display has been one of the most widely used screening methods for peptide/antibody drug discovery. Several phage display-derived biologics are already in the market, and the expiration of intellectual property rights of phage-display antibody discovery platforms suggests an increment in antibody drugs in the near future. This review summarizes the most common phage display libraries used in antiviral discovery, highlights the approaches employed to enhance the antiviral potency of selected peptides/antibody fragments, and finally provides a discussion about the present status of the developed antivirals in clinic.

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“… 2020 ; Bertoglio et al . 2021 ). Among the 12 selected antibodies, two of the RBD-specific antibodies (F61 and H121) had demonstrated high neutralizing activity and high affinity against SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants

Zhang

Sun

et al. 2021

Virol. Sin.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446–S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00409-4.

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SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface

Cited by 74 publications

References 85 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

Discovery of Antivirals Using Phage Display

Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants

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