CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma

Abstract SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed develop a strategy against variants. Here, we identified CD147 as universal receptor for its Meanwhile, Meplazeumab, humanized anti-CD147 antibody, could block cellular entry variants—alpha, beta, gamma, delta, with inhibition rates 68.7, 75.7, 52.1, 62.3% at 60 ?g/ml, respectively. Furthermore, transgenic mice were susceptible two variants, alpha beta. When infected, these developed exudative alveolar pneumonia, featured by responses involving alveoli-infiltrated macrophages, neutrophils, lymphocytes activation IL-17 signaling pathway. Mechanistically, proposed that severe COVID-19-related cytokine storm induced “spike protein-CD147-CyPA axis”: Infection through initiated JAK-STAT pathway, which further expression cyclophilin A (CyPA); CyPA reciprocally bound triggered MAPK Consequently, pathway regulated cytokines chemokines, promoted development storm. Importantly, Meplazumab effectively inhibit inflammation caused Therefore, our findings provided new perspective pathogenesis. validated variants can be targeted treatment.