近日, 洛克菲勒大学的Thomas Tuschl研究 团队在《Nature》杂志上发表题为“Small-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase”的研究论文。该研究发现 了一种非共价小分子抑制剂,可特异性靶向SARS-CoV-2 NSP14甲基转移酶,并通过高通量筛选识别了RU-0415529,随后经过多轮化学优化,开发出活性...
近日,洛克菲勒大学的Thomas Tuschl研究团队在《Nature》杂志上发表题为“Small-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase”的研究论文。该研究发现了一种非共价小分子抑制剂,可特异性靶向SARS-CoV-2 NSP14甲基转移酶,并通过高通量筛选识别了RU-0415529,随后经过多轮化学优化,开发出活性更强...
研究结果表明,TDI-015051作为一种具有高潜力的小分子药物,不仅在细胞实验中表现出强效的抗SARS-CoV-2活性,还在动物模型中有效降低了病毒负荷。通过靶向病毒RNA帽甲基转移酶NSP14,该研究为理解非竞争型抑制机制提供了新的视角,也为抗RNA病毒药物的设计提供了重要的理论依据和技术支持。
SARS-CoV-2COVID-19ExoribonucleaseDnaQ-like exonucleasesExonucleaseInhibitorsAlthough the global health emergency caused by SARS-CoV-2 has led to unprecedented health and socioeconomic crisis, as of today neither an antiviral treatment hCruz-González, Adrián...
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. The rapid development of highly effective vaccines2,3 against SARS-CoV-2 has altered the trajectory of the pandemic, and antiviral therapeutic
SARS-CoV-2Nonstructural protein 14 (NSP14)ZINC databaseDrug dockingThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat. This raises an urgent need for the development of effective drugs agai...
SARS-CoV-2, we searched for amino acid substitutions in nature that may interfere with nsp14 function. We found that viruses carrying a proline-to-leucine change at position 203 (P203L) have a high evolutionary rate and that a recombinant SARS-CoV-2 virus with the P203L mutation acquired ...
Therefore, our findings reveal a novel mechanism by which SARS-CoV-2 dysregulates the host antioxidant defense system and emphasize the vital role played by the SIRT1/NRF2 axis in host defense against SARS-CoV-2. 展开 关键词: SARS-CoV-2 NRF2 HMOX1 NSP14 SIRT1 Oxidative stress ...
Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of ...
Silhan, J., Klima, M., Otava, T.et al.Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase.Nat Commun14, 2259 (2023). https://doi.org/10.1038/s41467-023-38019-1 ...