Coronavirus disease 2019 (COVID-19) is a global pandemic and respiratory infection that has enormous damage to human lives and economies. It is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a non-pair-stranded positive-sense RNA virus. With increasing global threats and few therapeutic options, the discovery of new potential drug targets and the development of new therapy candidates against COVID-19 are urgently needed. Based on these premises, we conducted an analysis of transcriptomic datasets from SARS-CoV-2-infected patients and identified several SARS-CoV-2 infection signatures, among which TNFRSF5/PTPRC/IDO1/MKI67 appeared to be the most pertinent signature. Subsequent integrated bioinformatics analysis identified the signature as an important immunomodulatory and inflammatory signature of SARS-CoV-2 infection. It was suggested that this gene signature mediates the interplay of immune and immunosuppressive cells leading to infiltration-exclusion of effector memory T cells in the lungs, which is of translation relevance for developing novel SARS-CoV-2 drug and vaccine candidates. Consequently, we designed and synthesized a novel small-molecule quinoline derivative (RXn-02) and evaluated its pharmacokinetics in rats, revealing a peak plasma concentration (Cmax) and time to Cmax (Tmax) of 1.756 μg/mL and 0.6 h, respectively. Values of the area under the curve (AUC) (0-24 h) and AUC (0 h∼∞) were 18.90 and 71.20 μg h/mL, respectively. Drug absorption from the various regional segments revealed that the duodenum (49.84%), jejunum (47.885%), cecum (1.82%), and ileum (0.32%) were prime sites of RXn-02 absorption. No absorption was detected from the stomach, and the least was from the colon (0.19%). Interestingly, RXn-02 exhibited in vitro antiproliferative activities against hub gene hyper-expressing cell lines; A549 (IC50 = 48.1 μM), K-562 (IC50 = 100 μM), and MCF7 (IC50 = 0.047 μM) and against five cell lines originating from human lungs (IC50 range of 33.2-69.5 μM). In addition, RXn-02 exhibited high binding efficacies for targeting the TNFRSF5/PTPRC/IDO1/MK signature with binding affinities (ΔG) of -6.6, -6.0, -9.9, -6.9 kcal/mol respectively. In conclusion, our study identified a novel signature of SARS-CoV-2 pathogenesis. RXn-02 is a drug-like candidate with good in vivo pharmacokinetics and hence possesses great translational relevance worthy of further preclinical and clinical investigations for treating SARS-CoV-2 infections. Keywords: COVID-19 (Coronavirus disease 2019); Immunomodulation; Inflammation; Pharmacokinetics; SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。