Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern

Chaouat, Abigael Eva; Brizić, Ilija; Brlić, Paola Kučan; Atari, Nofar; Kliker, Limor; Alfi, Or; Mandelboim, Michal; Wolf, Dana; Tafish, Laith; Kol, Inbal; Jonjić, Stipan; Mandelboim, Ofer

doi:10.1016/j.isci.2022.104935

Cited by 13 publications

(9 citation statements)

References 54 publications

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“…The inhibitory effects of ACE2 ligands, but not of the product of its catalytic activity Ang(1-7), on TCR signaling and IS assembly support the notion that ACE2 limits CTL activation in a peptidase-independent fashion through signals triggered in response to ligand binding. Since anti-ACE2 Abs have been shown to be effective in limiting SARS-CoV-2 production in cellular and animal models ( Chen et al, 2021 ; Chaouat et al, 2022 ), our findings raise the possibility that using these Abs as therapeutics in COVID-19 patients may lead to unwanted immune suppression.…”

Section: Resultsmentioning

confidence: 83%

SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly

Onnis

Andreano

Cassioli

et al. 2022

Journal of Experimental Medicine

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CTL-mediated killing of virally infected or malignant cells is orchestrated at the immune synapse (IS). We hypothesized that SARS-CoV-2 may target lytic IS assembly to escape elimination. We show that human CD8+ T cells upregulate the expression of ACE2, the Spike receptor, during differentiation to CTLs. CTL preincubation with the Wuhan or Omicron Spike variants inhibits IS assembly and function, as shown by defective synaptic accumulation of TCRs and tyrosine phosphoproteins as well as defective centrosome and lytic granule polarization to the IS, resulting in impaired target cell killing and cytokine production. These defects were reversed by anti-Spike antibodies interfering with ACE2 binding and reproduced by ACE2 engagement by angiotensin II or anti-ACE2 antibodies, but not by the ACE2 product Ang (1-7). IS defects were also observed ex vivo in CTLs from COVID-19 patients. These results highlight a new strategy of immune evasion by SARS-CoV-2 based on the Spike-dependent, ACE2-mediated targeting of the lytic IS to prevent elimination of infected cells.

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Section: Resultsmentioning

confidence: 83%

SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly

Onnis

Andreano

Cassioli

et al. 2022

Journal of Experimental Medicine

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“…Previous studies have shown that soluble ACE2 directly binds to SARS-CoV-2 spike protein [16]. Many therapeutic approaches have emerged around ACE2, notably for its ability to bind SARS-CoV-2 and serve as a receptor for its entry into cells [9, 10, 27, 28]. Most of these approaches are limited to the use of ACE2 antibodies.…”

Section: Discussionmentioning

confidence: 99%

ACE2-Coated Virus-Like Particles Effectively Block SARS-CoV-2 Infection

Bayraktar,

Kayabolen,

Odabas

et al. 2023

Preprint

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A large body of research accumulated over the past three years dedicated to our understanding and fighting COVID-19. Blocking the interaction between SARS-CoV-2 Spike and ACE2 receptor has been considered an effective strategy as anti-SARS-CoV-2 therapeutics. In this study, we developed ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus. These ACE2-VLPs exhibited high neutralization capacity even when applied at low doses, and displayed superior efficacy compared to extracellular vesicles carrying ACE2, in the in vitro pseudoviral assays. ACE2-VLPs were stable under different environmental temperatures, and they were effective in blocking all tested variants of concern in vitro. Finally, ACE2-VLPs displayed marked neutralization capacity against Omicron BA.1 in the Vero E6 cells. Based on their superior efficacy compared to extracellular vesicles, and their demonstrated success against live virus, ACE2-VLPs can be considered as vital candidates for treating SARS-CoV-2. This novel therapeutic approach of VLP coating with receptor particles can serve as proof-of-concept for designing effective neutralization strategies for other viral diseases in the future.

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“…Viruses were isolated from positive nasopharyngeal swab samples.,. The viruses were propagated in Vero E6 cells 32 .…”

Section: Virusesmentioning

confidence: 99%

The selective effect of Ivermectin on different human coronaviruses; in-vitro study

Shahin,

Atari,

Meningher

et al. 2024

Preprint

Self Cite

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Background: The outbreak of coronavirus disease COVID-19, caused by Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has become an urgent public health concern worldwide. Although several clinical trials have pointed to new drugs with some anti-COVID-19 activity, we are far from having a safe and effective drug. In this study, we tested the effect of ivermectin on several coronaviruses (serotypes), including variants of SARS-CoV-2. Methods: The effect of ivermectin was tested on cells infected with four different coronaviruses: NL63 (Alphacoronavirus genus.), OC43, SARS-CoV-2, and Omicron (all Betacoronavirus genus). Two hours post-infection, different doses of ivermectin were added to the cell culture. Results: There was no effect of even a high dose of ivermectin on NL63, however, we found a significant effect on OC43 PFU with a 40% inhibition at a dose of 5M. The impact of ivermectin on SARS-CoV-2 and on its Omicron variant was much more pronounced and at a dose of 5M there was inhibition of 90% and 95% respectively. Discussion: Although coronaviruses have been recognized as human pathogens for more than 50 years, no effective treatment strategy exists. Our current study did not demonstrate any effect of ivermectin on Alphacoronavirus but it had a specific impact on the Betacoronavirus genus with a mild impact on OC43 and a decidedly pronounced effect on SARS-CoV-2 including its Omicron variant. Ivermectin should be further studied as a single agent or as part of combined treatment against Coronaviruses.

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Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern

Cited by 13 publications

References 54 publications

SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly

SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly

ACE2-Coated Virus-Like Particles Effectively Block SARS-CoV-2 Infection

The selective effect of Ivermectin on different human coronaviruses; in-vitro study

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