ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker

Chen, Yuning; Zhang, Yanan; Yan, Renhong; Wang, Guifeng; Zhang, Yuanyuan; Zhang, Zherui; Li, Yaning; Ou, Jianxia; Chu, Wendi; Liang, Zhijuan; Wang, Yongmei; Chen, Yili; Chen, Ganjun; Wang, Qi; Zhou, Qiang; Zhang, Bo; Wang, Chunhe

doi:10.1038/s41392-021-00740-y

Cited by 65 publications

(39 citation statements)

References 47 publications

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“…Together with our previous study, 5 our data suggest that 3E8 is potentially a potent and “broad-spectrum” blocker of multiple coronaviruses that utilize ACE2 as entry receptors, including SARS-CoV-2 Delta, Omicron, Alpha, Beta, Kappa, Gamma, SARS-CoV, and HCoV-NL63.…”

supporting

confidence: 84%

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ACE2-Targeting antibody suppresses SARS-CoV-2 Omicron and Delta variants

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

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supporting

confidence: 84%

“…3E8 also blocked the live SARS-CoV-2 infection of Vero E6 cells and in a prophylactic mouse model of COVID-19. 5 In this study, we showed that 3E8 could potentially block Delta and Omicron VOCs, demonstrating further that it was a potent and “broad-spectrum” blocker of all coronaviruses that utilize hACE2 as entry receptors.…”

mentioning

confidence: 60%

ACE2-Targeting antibody suppresses SARS-CoV-2 Omicron and Delta variants

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

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“…As a negative control, we also transfected VEEV-eGFP replicon RNA into naïve BHK-21 cells or BHK-21 cells pre-transfected with hACE2 expression plasmid, and only scattered GFP positive cells were detected at each time point post transfection ( Figure 4 (A), lower panel; Figure 4 (B)). For the antibody inhibition method, a neutralizing antibody against hACE2, 3E8 [ 35 ] was incubated with VEEV-SARS-CoV-2-S-eGFP replicating cells for 18 h. As shown in Figure 4 (C,D), the addition of 3E8 greatly reduced syncytium formation compared with the antibody-absent control. Collectively, these results provide strong evidence that VEEV-SARS-CoV-2-S-eGFP induced syncytium formation can mimic what the authentic SARS-CoV-2 does in a S- and receptor-dependent manner.…”

Section: Resultsmentioning

confidence: 99%

A new screening system for entry inhibitors based on cell-to-cell transmitted syncytia formation mediated by self-propagating hybrid VEEV-SARS-CoV-2 replicon

Chen

et al. 2022

Emerging Microbes & Infections

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The extremely high transmission rate of SARS-CoV-2 and severe cases of COVID-19 pose the two critical challenges in the battle against COVID-19. Increasing evidence has shown that the viral spike (S) protein-driven syncytia may be responsible for these two events. Intensive attention has thus been devoted to seeking S-guided syncytium inhibitors. However, the current screening campaigns mainly rely on either live virus-based or plasmid-based method, which are always greatly limited by the shortage of high-level biosafety BSL-3 facilities or too much labour-intensive work. Here, we constructed a new hybrid VEEV-SARS-CoV-2-S-eGFP reporter vector through replacement of the structural genes of Venezuelan equine encephalitis virus (VEEV) with the S protein of SARS-CoV-2 as the single structural protein. VEEV-SARS-CoV-2-S-eGFP can propagate steadily through cell-to-cell transmission pathway in S- and ACE2-dependent manner, forming GFP positive syncytia. In addition, a significant dose-dependent decay in GFP signals was observed in VEEV-SARS-CoV-2-S-eGFP replicating cells upon treatment with SARS-CoV-2 antiserum or entry inhibitors, providing further evidence that VEEV-SARS-CoV-2-S-eGFP system is highly sensitive to characterize the anti-syncytium-formation activity of antiviral agents. More importantly, the assay is able to be performed in a BSL-2 laboratory without manipulation of live SARS-CoV-2. Taken together, our work establishes a more convenient and efficient VEEV-SARS-CoV-2-S-eGFP replicating cells-based method for rapid screening of inhibitors blocking syncytium formation.

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“…The amino acid residues from W436 to Q506 inside RBD shape the Receptor Binding Motif (RBM), which carries 11 contact positions with ACE2 (5). The RBD region has received great attention, as it seems to be a major target of antibodies against the virus and other therapeutic interventions (6)(7)(8). In the RBD region, Omicron variant carries 15 mutations, 10 of which are identified in the RBM area (Fig.…”

Section: Omicron-specific C/h-crups That Belong To the Receptor Binding Domainmentioning

confidence: 99%

Prediction of SARS-CoV-2 Omicron Variant Immunogenicity, Immune Escape and Pathogenicity, through Analysis of Spike Protein-specific Core Unique Peptides

Pierros

Kontopodis

Stravopodis

et al. 2021

Preprint

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The recently discovered Omicron variant of the SARS-CoV-2 corona virus has raised a new, global, awareness, since it is considered as a new variant of concern from all major health organizations, including WHO and ECDC. Omicron variant is characterized by 30 amino acid changes, three small deletions and one small insertion in the Spike protein. In this study, we have identified the Core Unique Peptides (CrUPs) that reside exclusively in the Omicron variant of Spike protein and are absent from the human proteome, thus creating a new dataset of peptides named as C/H-CrUPs. Furthermore, we have analyzed their protein locations and compared them with the respective ones of Alpha and Delta SARS-CoV-2 variants. In Omicron, 115 C/H-CrUPs were generated and 119 C/H-CrUPs were lost, almost four times as many compared to the other two variants. From position 440 to position 508, at the Receptor Binding Motif (RBM), 8 mutations were detected, resulting in the construction of 28 novel C/H-CrUPs. Most importantly, in Omicron variant, new C/H-CrUPs carrying two or three mutant amino acids were produced, as a consequence of the accumulation of multiple mutations in the RBM. Remarkably, these Omicron-derived C/H-CrUPs that bear several mutated amino acids could not be recognized in any other viral Spike variant. We suggest that virus binding to the ACE2 receptor is facilitated by the herein identified C/H-CrUPs in contact point mutations and Spike-cleavage sites, while the immunoregulatory NF9 peptide is not detectably affected. Taken together, our findings indicate that Omicron variant contains intrinsic abilities to escape immune-system attack, while its mutations can mediate strong viral binding to the ACE2 receptor, leading to highly efficient fusion of the virus to the target cell. However, the intact NF9 peptide suggests that Omicron exhibits reduced pathogenicity compared to Delta variant.

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ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker

Cited by 65 publications

References 47 publications

ACE2-Targeting antibody suppresses SARS-CoV-2 Omicron and Delta variants

ACE2-Targeting antibody suppresses SARS-CoV-2 Omicron and Delta variants

A new screening system for entry inhibitors based on cell-to-cell transmitted syncytia formation mediated by self-propagating hybrid VEEV-SARS-CoV-2 replicon

Prediction of SARS-CoV-2 Omicron Variant Immunogenicity, Immune Escape and Pathogenicity, through Analysis of Spike Protein-specific Core Unique Peptides

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