Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

Huijie Bian; Zhao-Hui Zheng; Ding Wei; Zheng Zhang; Wen-Zhen Kang; Chun-Qiu Hao; Ke Dong; Wen Kang; Jie-Lai Xia; Jin-Lin Miao; Rong-Hua Xie; Bin Wang; Xiu-Xuan Sun; Xiang-Min Yang; Peng Lin; Jie-Jie Geng; Ke Wang; Hong-Yong Cui; Kui Zhang; Xiao-Chun Chen; Hao Tang; Hong Du; Na Yao; Shuang-Shuang Liu; Lin-Na Liu; Zhe Zhang; Zhao-Wei Gao; Gang Nan; Qing-Yi Wang; Jian-Qi Lian; Zhi-Nan Chen; Ping Zhu

Angiotensin-converting enzyme 2 (ACE2) is the only reported host cellular receptor for SARS-CoV-2 to our knowledge, 11 which presents in various human tissues, including alveolar epithelial cells, endothelial cells of arteries and veins, smooth muscle cells, etc. 12 Our current published data showed a direct interaction between spike protein of SARS-CoV-2 and CD147, a type I transmembrane glycoprotein expressed on epithelial cells. A humanized IgG2 monoclonal antibody against CD147, meplazumab, effectively inhibited SARS-CoV-2 replication and virus-induced cytopathic effect in Vero E6 cells, both in a dose-dependent manner. These data demonstrated a novel entry of virus infection mediated by CD147 receptor. 13 CD147 is also presented in activated inflammatory cells and participates the regulation of cytokine secretion and leukocytes chemotaxis by binding with cyclophilin A (CyPA). 14, 15 CyPA is a proinflammatory cytokine that is up-regulated in response to virus infection. 16 Our previous studies demonstrated that antibody targeting CD147 inhibited CyPA-induced T cell chemotaxis thus attenuating the local inflammation. 17 Based on these evidences, we assess the clinical outcomes using meplazumab as add-on therapy in patients with COVID-19 pneumonia. We designed an open-label, concurrent controlled trial to evaluate whether meplazumab infusion improves the patients with COVID-19 pneumonia by inhibiting virus replication and suppressing inflammation. We hope our study will shed light on finding a new drug and strategy to All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.