Article
Virology
Hsu-Feng Chu, Shu-Chun Cheng, Chiao-Yin Sun, Chi-Yuan Chou, Ta-Hsien Lin, Wei-Yi Chen
Summary: In this study, the crystal structure of porcine epidemic diarrhea virus (PEDV) papain-like protease 2 (PLP2) in complex with ubiquitin (Ub) was reported. The analysis revealed the interactions between PEDV PLP2 and the Ub substrate. Furthermore, the study identified key residues and a conformational feature of PEDV PLP2 that contribute to its function. These findings provide structural insights into the mechanistic effects of PEDV PLP2.
JOURNAL OF VIROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Anastasiia I. Petushkova, Lyudmila V. Savvateeva, Andrey A. Zamyatnin
Summary: Papain-like cysteine proteases are widely expressed enzymes that regulate protein turnover in lysosomes. Recent discoveries have shown that these proteases also have specific functions in different organelles and extracellular environments. Human cysteine cathepsins are the most studied proteases in this family and are involved in both physiological and pathological processes. The specificity of each protease to its substrates is determined by the structure of the binding cleft and the amino acid motifs in this region.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Immunology
Shasha Li, Zixiang Zhu, Fan Yang, Weijun Cao, Jinping Yang, Caina Ma, Zhenxiang Zhao, Hong Tian, Xiangtao Liu, Junwu Ma, Shaobo Xiao, Haixue Zheng
Summary: In this study, the researchers identified the PEDV membrane (M) protein as a new antagonist of type I IFN production, revealing a novel antagonistic mechanism employ by PEDV to inhibit type I IFN production by targeting IRF7. The interaction between PEDV M protein and IRF7 were found to significantly suppress TBK1/IKK epsilon-induced IRF7 phosphorylation and dimerization, ultimately leading to decreased expression of type I IFN.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maude Giroud, Bernd Kuhn, Wolfgang Haap
Summary: This review article summarizes the drug discovery efforts in the research community from 2017 to 2022, focusing on the optimization of small molecule cysteine protease inhibitors and in vivo studies. Although potent and selective inhibitors for neglected tropical diseases have been identified, none of them have reached the stage of active clinical development.
CURRENT MEDICINAL CHEMISTRY
(2023)
Review
Virology
Varada Anirudhan, Hyun Lee, Han Cheng, Laura Cooper, Lijun Rong
Summary: The review provides information on potential treatment strategies for COVID-19 that target the essential proteins of the virus, specifically 3CL(pro) and PLpro, which are key in inhibiting viral replication and may offer insights from previous experience with SARS-CoV.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Engineering, Environmental
Qizhi Liang, Yue Huang, Minghui Wang, Deqi Kuang, Jiahua Yang, Yongxiang Yi, Hai Shi, Jinlong Li, Jie Yang, Genxi Li
Summary: In this study, an electrochemical biosensor was developed for the detection of SARS-CoV-2 using its papain-like cysteine protease (PLpro), as well as for screening protease inhibitors against the virus. The biosensor allows sensitive and specific detection of SARS-CoV-2 PLpro in complex real environments and has been tested with patient samples to demonstrate its practical application capability. Additionally, rapid screening of inhibitors against SARS-CoV-2 PLpro can also be achieved, highlighting the potential of this electrochemical biosensor in COVID-19 combat and drug development.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Plant Sciences
Yanlei Zhai, Yuanyuan Cui, Miaoyu Song, Alexander Vainstein, Shangwu Chen, Huiqin Ma
Summary: The papain-like cysteine proteases (PLCPs) play essential roles in plant stress responses, growth, and senescence. In this study, 31 PLCP genes were identified in the fig genome, and were categorized into nine subfamilies. Subcellular localization analysis revealed different targeting of PLCP proteins. RNA-seq and proteome analyses provided insights into the expression and abundance characteristics of FcPCLPs in different parts of the fig plant.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Hangchen Hu, Qian Wang, Haixia Su, Qiang Shao, Wenfeng Zhao, Guofeng Chen, Minjun Li, Yechun Xu
Summary: This study discovered two activators of SARS-CoV-2 PLpro and identified a unique allosteric and covalent regulatory site. These findings provide insights into the allosteric modulation of SARS-CoV-2 PLpro and offer a potential target for allosteric inhibitors design.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Chia-Chuan Cho, Shuhua G. Li, Tyler J. Lalonde, Kai S. Yang, Ge Yu, Yuchen Qiao, Shiqing Xu, Wenshe Ray Liu
Summary: SARS-CoV-2 encodes PLPro which not only suppresses host immune responses but also serves as a potential therapeutic target. Experimental screening identified several inhibitors with strong inhibitory effects on PLPro, among which SJB2-043 exhibits unique characteristics that warrant further investigation.
Article
Food Science & Technology
Dong-Yu Shen, Nabila Begum, Huan-Lu Song, Yu Zhang, Li-Jin Wang, Yi-Jia Zhao, Lei Zhang, Peng Liu
Summary: The study showed that peptides with <1 kDa molecular weight purified from porcine bone protein extracts have good in vitro antioxidant activity and umami score. In vivo studies demonstrated significant antioxidant activity and dose-dependent differences compared to the control group for these peptides fractions.
Article
Microbiology
Xiaozhen Guo, Kejian Yu, Zhonghao Xin, Liping Liu, Yuehua Gao, Feng Hu, Xiuli Ma, Kexiang Yu, Yufeng Li, Bing Huang, Zhengui Yan, Jiaqiang Wu
Summary: This study found that PEDV-infected cells contain SGs and are resistant to SA-induced SGs formation. PEDV infection disrupts SGs formation by downregulating G3BP1 expression. PEDV replication is significantly enhanced when SGs assembly is impaired by silencing G3BP1.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Vera J. E. van Vliet, Nhan Huynh, Judith Pala, Ankoor Patel, Alex Singer, Cole Slater, Jacky Chung, Mariska van Huizen, Joan Teyra, Shane Miersch, Gia-Khanh Luu, Wei Ye, Nitin Sharma, Safder S. Ganaie, Raquel Russell, Chao Chen, Mindy Maynard, Gaya K. Amarasinghe, Brian L. Mark, Marjolein Kikkert, Sachdev S. Sidhu
Summary: In this study, researchers have identified ubiquitin variants (UbVs) that can specifically and effectively block the activity of the papain-like protease (PLpro) in SARS-CoV-2. These UbVs inhibit the essential cleavage activities of the protease, reducing viral replication and providing a potential therapeutic approach for combating coronaviruses.
Review
Chemistry, Medicinal
C. S. Brian Chia, Siew Pheng Lim
Summary: This literature review discusses the patents of coronavirus PLpro inhibitors, providing an overview of the inhibitors that have generated commercial interest, particularly among drug companies.
Article
Biotechnology & Applied Microbiology
Chang Woo Kwon, Bokyong Chung, Sang-Ho Yoo, Pahn-Shick Chang
Summary: This study evaluated the expression of recombinant papain-like cysteine protease inhibitors in the Escherichia coli Rosetta (DE3) system, and determined the inhibition mode of the expressed inhibitors. SnuCalCpI08 and SnuCalCpI17 were successfully expressed in this system, with SnuCalCpI17 showing a slow-binding inhibition mode in papain inhibition assay.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Natalia Balbinott, Rogerio Margis
Summary: The regulation of protease activity is crucial for plant growth and development. Plant cystatins, inhibitors of cysteine proteases, have unique structural and functional diversity. The gene structure of plant cystatins is highly conserved in Viridiplantae, providing insights into their evolutionary relationships. Multiple gene duplication events, intron losses, and gains have been identified during the expansion and diversity of the phytocystatin family.