更新于：2024-11-01

norovirus 3CL protease x SARS-CoV-2 3CLpro

更新于：2024-11-01

基本信息

关联

项与 norovirus 3CL protease x SARS-CoV-2 3CLpro 相关的药物

GC-376

靶点

SARS-CoV-2 3CLpro x norovirus 3CL protease

作用机制

SARS-CoV 3CLpro抑制剂 [+1]

在研机构

Anivive Lifesciences, Inc.初创企业

原研机构

Kansas State University

在研适应症

新型冠状病毒感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 norovirus 3CL protease x SARS-CoV-2 3CLpro 相关的临床结果

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100 项与 norovirus 3CL protease x SARS-CoV-2 3CLpro 相关的转化医学

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0 项与 norovirus 3CL protease x SARS-CoV-2 3CLpro 相关的专利（医药）

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项与 norovirus 3CL protease x SARS-CoV-2 3CLpro 相关的文献（医药）

2024-02-01·Steroids

Design, synthesis and biological evaluation of betulinic acid derivatives as potential inhibitors of 3CL-protease of SARS-CoV-2

Article

作者: Nie, Tianqing ; Xu, Yechun ; Wu, Wanying ; Zhang, Zijia ; Long, Huali ; Hou, Jinjun ; Liu, Yaowen ; Lei, Min

During the coronavirus reproduction process, 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are accountable for the fragmentation of two polyprotein precursors (pp1a/pp1ab) into substructural proteins. These two proteins are vital for the replication and transcription of the viral genome. Therefore, 3CLpro is a key protein and target for the design of coronavirus inhibitors. In previous studies, we found that betulinic acid has an inhibitory effect on 3CLpro, with 51.5 % inhibition of 3CLpro at 20 µM. Then, series of betulinic acid derivatives were designed, synthesized, and evaluated for their inhibition activities. The results showed that BA02 and BA05 showed significant inhibitory activity on 3CLpro with inhibitory rates of 78.1 % and 82.5 % at 20 µM, respectively. Further evaluation of these two compounds shows that their IC₅₀ values are 7.22 ± 0.14 μM and 6.40 ± 0.14 μM, respectively.

2023-05-24·International journal of molecular sciences

Eupatin, a Flavonoid, Inhibits Coronavirus 3CL Protease and Replication.

Article

作者: Park, Junsoo ; Park, Yea-In ; Kim, Jang Hoon ; Lee, Ik Soo ; Lee, Siyun

The coronavirus disease 2019 (COVID-19) pandemic has caused more than six million deaths worldwide since 2019. Although vaccines are available, novel variants of coronavirus are expected to appear continuously, and there is a need for a more effective remedy for coronavirus disease. In this report, we isolated eupatin from Inula japonica flowers and showed that it inhibits the coronavirus 3 chymotrypsin-like (3CL) protease as well as viral replication. We showed that eupatin treatment inhibits SARS-CoV-2 3CL-protease, and computational modeling demonstrated that it interacts with key residues of 3CL-protease. Further, the treatment decreased the number of plaques formed by human coronavirus OC43 (HCoV-OC43) infection and decreased viral protein and RNA levels in the media. These results indicate that eupatin inhibits coronavirus replication.

2022-06-01·Virology3区 · 医学

Norovirus 3C-Like protease antagonizes interferon-β production by cleaving NEMO

3区 · 医学

Article

作者: Zhou, Yanrong ; Zhu, Xinyu ; Xiao, Shaobo ; Chen, Zeliang ; Wang, Dang ; Zhang, Huan ; Jiang, Pengfei ; Fang, Liurong

An epidemic owing to Norovirus (NoV) has recently been occurring worldwide. Severe cases of NoV can lead to patient death, resulting in significant public health problems. In the early stages of infection, antagonizing the production of host interferon (IFN) is an important strategy for viruses to establish infection. However, the relationship between NoV and interferon and its mechanism remains unclear. In this study, the 3C-like protease encoded by NoV was found to effectively suppress Sendai virus (SEV)-mediated IFN-β production by cleaving the NF-κB essential modulator (NEMO). Glutamine 205 is the site of NoV3CL^pro-mediated cleavage of NEMO and this cleavage suppresses the ability of NEMO to activate downstream IFN production. These findings demonstrate that NoV3CL^pro-induced cleavage limits NEMO to the activation of type I IFN signaling. In summary, our findings indicate that NoV3CL^pro is a new interferon antagonist, and enhances our understanding of the escape of innate immunity mediated by NoV3CL^pro.