CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma
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Abstract
SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants—alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 μg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a “spike protein-CD147-CyPA signaling axis”: Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.
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SciScore for 10.1101/2021.05.14.444111: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Multiplex immunofluorescence staining: Multiplex immunofluorescence analyses were performed using 3-μm-thick sections of formalin-fixed and paraffin-embedded tissues. Table 2: Resources
Antibodies Sentences Resources For CD147 antibody treatment, 3 mg/kg CD147 antibody (Meplazumab) was administered via the tail vein at 1 d.p.i. CD147suggested: NoneA mouse anti-human CyPA antibody (50 μg) and mouse anti-human CD147 antibody (Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, China, 50 μg) were used for antibody immobilization. anti-hu…SciScore for 10.1101/2021.05.14.444111: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Multiplex immunofluorescence staining: Multiplex immunofluorescence analyses were performed using 3-μm-thick sections of formalin-fixed and paraffin-embedded tissues. Table 2: Resources
Antibodies Sentences Resources For CD147 antibody treatment, 3 mg/kg CD147 antibody (Meplazumab) was administered via the tail vein at 1 d.p.i. CD147suggested: NoneA mouse anti-human CyPA antibody (50 μg) and mouse anti-human CD147 antibody (Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, China, 50 μg) were used for antibody immobilization. anti-human CyPAsuggested: Noneanti-human CD147suggested: NoneThe images were developed following incubation with the secondary antibody (goat anti-mouse IgG (H+L), 31430, Thermo Fisher Scientific, 1:5000 dilution) at room temperature for 1 h. anti-mouse IgGsuggested: (Thermo Fisher Scientific Cat# 31430, RRID:AB_228307)Experimental Models: Cell Lines Sentences Resources Generation of stable knockdown and knockout cell lines: VeroE6 cells were transfected with supernatants containing lentiviruses encoding the shCD147 and shACE2 constructs (GeneChem Co. Ltd.) using Lipofectamine 2000 reagent (Invitrogen) to generate the CD147 and ACE2 knockdown cell lines, respectively. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Software and Algorithms Sentences Resources GenePix, ScanArray Express, ArrayVision and MicroVigene). MicroVigenesuggested: (MicroVigene, RRID:SCR_002820)Statistical analyses were performed using GraphPad Prism, version 8.0. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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