2021-05-30

National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. hjbian@fmmu.edu.cn.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; College of Military Preventive Medicine, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Department of Pathology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; College of Military Preventive Medicine, Fourth Military Medical University, Xi'an, China.; Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, Changzhou, China.; Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, Changzhou, China.; Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, Changzhou, China.; Department of Foreign Languages, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. znchen@fmmu.edu.cn.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. zhuping@fmmu.edu.cn.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG(2) monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C(max) and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between