To identify the function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome (SARS) coronavirus (CoV), we analyzed the protein-protein interaction among HAb18G/CD147, cyclophilin A (CyPA), and SARS-CoV structural proteins by coimmunoprecipitation and surface plasmon resonance analysis. Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147. Further research showed that HAb18G/CD147, a transmembrane molecule, was highly expressed on 293 cells and that CyPA was integrated with SARS-CoV. HAb18G/CD147-antagonistic peptide (AP)-9, an AP of HAb18G/CD147, had a high rate of binding to 293 cells and an inhibitory effect on SARS-CoV. These results show that HAb18G/CD147, mediated by CyPA bound to SARS-CoV N protein, plays a functional role in facilitating invasion of host cells by SARS-CoV. Our findings provide some evidence for the cytologic mechanism of invasion by SARS-CoV and provide a molecular basis for screening anti-SARS drugs.

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Both MSCs and MSC-chondrocytes suppressed CII-reactive T-cell responses to CII in RA, which suggested that MSCs could be a potential candidate for RA treatment in future if further confirmed in vivo.

In December 2019, a number of patients with a new type of pneumonia of unknown etiology were detected in Wuhan, China. (1) It was then soon determined that it was a new severe acute respiratory syndrome (SARS) that was caused by a new coronavirus, the SARS-CoV-2 virus. (2) The new pneumonia was later named the Novel 2019 Coronavirus or COVID-19. (3) In 2002-2003, another SARS-causing coronavirus, the SARS-CoV virus, caused one of the most deadly epidemics in recent history. The outbreak of SARS-CoV caused more than 8,000 reported cases and 774 deaths, with a case-fatality rate (CFR) of 7% in China. (4) Less than a decade later in 2012, another coronavirus, the Middle-East respiratory syndrome (MERS) virus, the MERS-CoV virus, emerged. (5) An outbreak of this virus in 2014 resulted in 662 reported cases and a CFR of 32.97%. (6) Together, these had informed us that coronaviruses represent a new kind of viral pathogens that are characterized by their ability to cause

AbstractsRecent 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 IgG2 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 Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

In this study, a novel Al 18 F-NOTA-FAPI probe was developed for fibroblast activation protein (FAP) targeted tumour imaging, which was available to achieve curie level radioactivity by automatic synthesizer. The tumour detection efficacy of Al 18 F-NOTA-FAPI was further validated both in preclinical and clinical translational studies. MethodsThe radiolabeling procedure of Al 18 F-NOTA-FAPI was optimized. Cell uptake and competitive binding assay were completed with U87MG and A549 cell lines, to evaluate the affinity and specificity of Al 18 F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of Al 18 F-NOTA-FAPI probe were researched with healthy Kunming (KM) and/or U87MG model mice.After the approval of ethical committee, Al 18 F-NOTA-FAPI probe was translated into clinical for the PET/CT imaging of first 10 cancer patients. ResultsThe radiolabeling yield of Al 18 F-NOTA-FAPI was 33.8 ± 3.2% through manually operation (n = 10), with the radiochemical purity over than 99% and the specific activity of 9.3-55.5 MBq/nmol. Whole body effective dose of Al 18 F-NOTA-FAPI was estimated to be 1.24E-02 mSv/MBq, lower than several other FAPI probes ( 68 Ga-FAPI-04, 68 Ga-FAPI-46 and 68 Ga-FAPI-74). In U87MG tumour bearing mice, Al 18 F-NOTA-FAPI showed good tumor detection efficacy from the results of micro PET/CT imaging and biodistribution studies. In organ biodistribution study of human patients, Al 18 F-NOTA-FAPI showed lower SUVmean than 2-[ 18 F]FDG in most organs, especially in liver (1.1 ± 0.2 vs. 2.0 ± 0.9), brain (0.1 ± 0.0 vs. 5.9 ± 1.3), and bone marrow (0.9 ± 0.1 vs. 1.7 ± 0.4). Meanwhile, Al 18 F-NOTA-FAPI do not show extensive bone uptakes, and was able to find out more tumour lesions than 2-[ 18 F]FDG in the PET/CT imaging of several patients. ConclusionAl 18 F-NOTA-FAPI probe was successfully fabricated and applied in fibroblast activation protein targeted tumour PET/CT imaging, which showed excellent imaging quality and tumour detection efficacy in U87MG tumour bearing mice as well as in human cancer patients.

Background: 68 Ga-NOTA-WL12 is a peptide-based positron emission tomography (PET) imaging agent. We conducted a first-in-human study of 68 Ga-NOTA-WL12 for PET to study the in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying programmed death ligand-1 (PD-L1) expression levels in advanced non-small cell lung cancer (NSCLC) patients. Methods: In vitro assessment of the PD-L1 expression and cellular uptake of 68 Ga-NOTA-WL12 were performed, followed by in vivo evaluation of 68 Ga-NOTA-WL12 uptake in mouse models with tumors. Nine NSCLC patients with lesions expressing PD-L1 were enrolled and monitored for adverse events during the study. 68 Ga-NOTA-WL12 and paired 18 F-FDG PET/CT imaging were performed. Uptake (SUV/L and kBq/mL) values of tumors and normal organs were obtained.Radiopharmaceutical biodistribution, radiation dosimetry and the relationship of tumor uptake to PD-L1 expression were evaluated. Follow-up 18 F-FDG PET/CT was performed in patients who had undergone treatment with a combination of pembrolizumab with chemotherapy. Results: 68 Ga-NOTA-WL12 exhibited PD-L1 specific uptake in vitro and in PD-L1-positive tumors in vivo. 68 Ga-NOTA-WL12 PET imaging proved safe with acceptable radiation dosimetry. Physiological tracer uptake was mainly visible in the liver, spleen, small intestine and kidney. Tumors were clearly visible, particularly in the lungs, with a T/lung ratio of 4.45 ±1.89 at 1 h. One hour was a suitable time-point for image acquisition because no significant differences were noted in tumor-to-background ratios between 1 and 2 h. A strong, positive correlation was found between tumor uptake (SUVpeak) and PD-L1 immunohistochemistry results (r = 0.9349; P = 0.002). 68 Ga-NOTA-WL12 and 18 F-FDG PET studies suggest that PD-L1 PET before therapy may indicate the therapeutic efficacy of pembrolizumab plus chemotherapy combination treatment. Conclusions: Our first-in-human findings demonstrate the safety and feasibility of 68 Ga-NOTA-WL12 for noninvasive, in vivo detection of tumor PD-L1 expression levels, indicating potential benefits for clinical PD-L1 therapy.

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