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10.1038/s41392-021-00760-8

http://scihub22266oqcxt.onion/10.1038/s41392-021-00760-8
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suck abstract from ncbi


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pmid34564690      Signal+Transduct+Target+Ther 2021 ; 6 (1): 347
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  • CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma #MMPMID34564690
  • Geng J; Chen L; Yuan Y; Wang K; Wang Y; Qin C; Wu G; Chen R; Zhang Z; Wei D; Du P; Zhang J; Lin P; Zhang K; Deng Y; Xu K; Liu J; Sun X; Guo T; Yang X; Wu J; Jiang J; Li L; Zhang K; Wang Z; Zhang J; Yan Q; Zhu H; Zheng Z; Miao J; Fu X; Yang F; Chen X; Tang H; Zhang Y; Shi Y; Zhu Y; Pei Z; Huo F; Liang X; Wang Y; Wang Q; Xie W; Li Y; Shi M; Bian H; Zhu P; Chen ZN
  • Signal Transduct Target Ther 2021[Sep]; 6 (1): 347 PMID34564690show ga
  • 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 mug/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.
  • |*COVID-19 Drug Treatment[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics/*metabolism[MESH]
  • |Animals[MESH]
  • |Antibodies, Monoclonal, Humanized/*pharmacology[MESH]
  • |Basigin/*antagonists & inhibitors/genetics/*metabolism[MESH]
  • |COVID-19/genetics/*metabolism[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Cytokine Release Syndrome/*drug therapy/genetics/metabolism[MESH]
  • |Humans[MESH]
  • |MAP Kinase Signaling System/drug effects/genetics[MESH]
  • |Mice[MESH]
  • |Mice, Transgenic[MESH]
  • |SARS-CoV-2/genetics/*metabolism[MESH]


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