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您的检索式：作者名="Chunting Qi"
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| 1 | SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation显示文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is the ongoing global pandemic that poses substantial challenges to public health worldwide.A subset of COVID-19 patients experience systemic inflammatory response,known as cytokine storm,which may lead to death.Receptor-interacting serine/threonine-protein kinase 1(RIPK1)is an important mediator of inflammation and cell death.Here,we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection.We found evidence of RIPK1 activation in human COVID-19 lung pathological samples,and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2.Inhibition of RIPK1 using multiple smallmolecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids.Furthermore,therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load,and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice.Mechanistically,we found that the RNA-dependent RNA polymerase of SARS-CoV-2,NSP12,a highly conserved central component of coronaviral replication and transcription machinery,promoted the activation of RIPK1.Furthermore,NSP12323L variant,encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy,Italy,that carries a Pro323Leu amino acid substitution in NSP12,showed increased ability to activate RIPK1.Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells.Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19. | Gang Xu Ying Li Shengyuan Zhang Haoran Peng Yunyun Wang Dekang Li Taijie Jin Zhuohao He Yilun Tong Chunting Qi Guowei Wu Kangyun Dong Jizhou Gou Yang Liu Tongyang Xiao Jing Qu Liang Li Liang Liu Ping Zhao Zheng Zhang Junying Yuan | 2021 | Cell Research2021，31，12： | 6 |
| 2 | Structure-based development of potent and selective type-II kinase inhibitors of RIPK1显示文摘Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical evaluation.Recently,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.Here,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i.We also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62,which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases.Collectively,62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development. | Ying Qin Dekang Li Chunting Qi Huaijiang Xiang Huyan Meng Jingli Liu Shaoqing Zhou Xinyu Gong Ying Li Guifang Xu Rui Zu Hang Xie Yechun Xu Gang Xu Zheng Zhang Shi Chen Lifeng Pan Ying Li Li Tan | 2024 | Acta Pharmaceutica Sinica B2024，14，1： | 0 |
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