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On March 14, a research team from the Fourth Military Medical University published an article on the preprint platform bioRxiv, revealing a new way for the new coronavirus (SARS-CoV-2) to invade host cells: CD147-spike protein (SP)CD147, also known as Basigin or EMMPRIN, is a transmembrane glycoprotein that belongs to the immunoglobulin superfamilySince previous studies have shown that CD147 plays a functional role in facilitating SARS-CoV intrusion into host cells, and that CD147 antagonistic peptide-9 has an inhibitory effect on SARS-CoV, the team decided to investigate the possible role of CD147 in the new coronavirus intrusion host cells, considering the similarity between SARS-CoV and SARS-CoV-2Meplazumab inhibits SARS-CoV-2 replication (source: bioRxiv)study found that SP binds to the receptor CD147 on host cells to mediate virus invasionIn in vitro antiviral tests, anti-CD147 humanized antibody meplazumab significantly inhibited the virus from invading host cells (EC50 was 24.86 ?g/mL; IC50 was 15.16 ?g/mL)Immune coprecipitation and ELISA also confirm the combination of the two proteinsIn addition, through an immunoelectron microscope, the team observed the location of CD147 and S proteins in Vero E6 cells infected with SARS-CoV-2 infectionThese findings suggest that CD147 may be a key target for the development of specific anti-SARS-CoV-2 drugsbased on the above findings, a team from the Fourth Military Medical University conducted a clinical trial (NCT04275245) to investigate the effectiveness and safety of CD147 antibody meplazumab as a "complementary therapy" for the treatment of COVID-19 patientsspecifically,, in this trial, all patients received treatment strategies recommended in the New Coronary Virus Pneumonia Treatment Program, issued by the National Health Board, including antiviral therapy, glucocorticoid therapy, and antibiotic therapyEligible patients supplement 10 mg meplazumab intravenously on the first, second, and fifth daysThe end point of the test includes the virus removal rate, the severity of the case, etcsource: medRxivOn March 24, the team published the results of the experiment on the preprint platform medRxivFrom February 3 to February 10, 2020, 17 patients (4 common, 6 heavy, 7 critical) were recruited and assigned to the meplazumab group, and 11 hospitalized patients (4 general, 4 heavy, 3 critical) were recruited and assigned to the meplazumab group as a simultaneous control Baseline characteristics were basically balanced in both groups of patients in terms of efficacy, the overall improvement rate for the 7th, 14th, 21st and 28th days of follow-up in the meplazumab group (defined as the proportion of patients discharged from hospital or improved in severity of the disease) was 17.6% (3/17), 47.1% (8/17), 82.4% (1 4/17) and 94.1% (16/17), with corresponding data in the control group 0% (0/11), 27.3% (3/11), 54.5% (6/11) and 81.8% (9/11) Compared to the control group, meplazumab treatment significantly improved discharge and case severity of heavy and critically ill patients (see figure below) source: medRxiv test also assessed the virus removal by detecting transnegative rates and transnegative times On the 7th day, the transnegative rates of the meplazumab group and the control group were 76.5% (13/17) and 27.3% (3/11), respectively, and on the 14th day, the transnegativeity rates of the meplazumab group and the control group were 94.1% (16/17) and 54.4% (6/11), respectively The time for detection of virus nucleic acid in the Meplazumab group was 3 days in the median, significantly shorter than that of the control group (median 13 days) All of this data show that meplazumab therapy has significant benefits in removing SARS-CoV-2 (see chart below) source: medRxiv In addition, the concentration of lymphocytes and C-reactive proteins in the meplazumab group returned to normal patient severity increased significantly and rapidly (below) source: medRxiv safety aspects, meplazumab treatment of patients did not show adverse reactions based on these data and information, the researchers believe that meplazumab has been effective in improving the rehabilitation of COVID-19 patients and has good safety These results support a larger study to investigate the potential of meplazumab as a treatment option for COVID-19 the discussion section of the paper also points out that CD147 is also a receptor for the ligand CyPA, and that their interaction is key to inflammation and towards the chemicalization Therefore, the researchers hypothesized that meplazumab could also block the interaction between CyPA and CD147 and inhibit the inflammatory response Special Note: According to medRxiv's statement, articles published on the platform have not been peer-reviewed and these medical advances have yet to be evaluated and should not be used to guide clinical practice References: Ke Wang et al SARS-CoV-2 invades host cells via a novel route: CD147-spike protein.
Huijie Bian et al Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-onclinical trial.