Article
Virology
Yuan Fang, Chang Wang, Chong Wang, Ruyi Yang, Peng Bai, Xue-Yi Zhang, Jing Kong, Lei Yin, Yang Qiu, Xi Zhou
Summary: Enteroviruses, including important human pathogens like EV-A71, coxsackieviruses, and echoviruses, pose a significant threat to global public health. Targeting the helicase activity of Enteroviral 2C with designed peptides, such as 2CL and B-2CL, show promising potential as broad-spectrum antiviral drugs against enteroviruses, offering strong in vitro and in vivo antiviral efficacy.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Anthony D. Rish, Zhangfei Shen, Zhenhang Chen, Nan Zhang, Qingfei Zheng, Tian-Min Fu
Summary: This study reports two cryo-EM structures of RuvB, revealing the mechanism of HJ branch migration. RuvB assembles into a spiral staircase, ring-like hexamer, enveloping double-stranded DNA. The asymmetric assembly of RuvB explains the 6:4 stoichiometry of the RuvB/RuvA complex in coordinating HJ migration in bacteria. These findings provide a mechanistic understanding of HJ branch migration facilitated by RuvB, which may be universally shared by prokaryotic and eukaryotic organisms.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Yu-Ting Liao, Huey-Pin Tsai, Shih-Min Wang, Shun-Hua Chen
Summary: The study demonstrated that 6-OHDA treatment in EV71-infected mice increased the survival rate and decreased clinical scores. Additionally, 6-OHDA treatment resulted in decreased levels of NE, epinephrine, dopamine, and interferon-gamma in plasma. Furthermore, there were significant increases in certain immune cell populations in the peripheral blood and spleen after 6-OHDA treatment in infected mice.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Applied
Minyeong Kim, Seong-Ryeol Kim, Jiye Park, Seo-Hyeon Mun, Myounghai Kwak, Hyun-Jeong Ko, Seung-Hoon Baek
Summary: This study aimed to investigate the structure and anti-enterovirus 71 (EV71) effects of polysaccharides extracted from the roots of Sanguisorba officinalis (SO), traditionally used for infectious diseases. The results showed that the purified polysaccharide (S-a3) significantly inhibited cell death and viral gene expression in EV71-infected cells, and alleviated EV71-induced symptoms in a mouse model. The effective dose of S-a3 was non-toxic. This study demonstrates that polysaccharides from SO can be a safe and effective treatment for EV71 infection.
CARBOHYDRATE POLYMERS
(2022)
Article
Biochemistry & Molecular Biology
Naifu Zhang, Keith J. Olsen, Darby Ball, Sean J. Johnson, Sheena D'Arcy
Summary: Using various techniques, this study characterized the interaction between Mtr4 and different RNAs. The results revealed consistent interactions between the helicase core of Mtr4 and various RNAs, as well as novel interactions between a region of the arch domain and RNA. These interactions play a crucial role in RNA unwinding and modulate Mtr4's discrimination between different RNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Virology
Xiaohui Zhao, Huijun Yuan, Hang Yang, Yan Liu, Meng Xun, Xiaozhen Li, Tingting Fan, Bo Wu, Shangrui Guo, Hongliang Wang
Summary: EV71 is a common pathogen causing hand, foot, and mouth disease in young children, and it is associated with severe neurological complications. This study found that the ER-resident acetyltransferase NAT8 is a host factor for EV71 infection and promotes viral replication by interacting with viral proteins.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Natalia I. Romanenkova, Thi Thanh Thao Nguyen, Liudmila N. Golitsyna, Natalia V. Ponomareva, Nadezhda R. Rozaeva, Olga I. Kanaeva, Artem V. Leonov, Nadezhda A. Novikova, Maina A. Bichurina
Summary: In South Vietnam, a high proportion of enterovirus 71 (EVA71) was found in cases of hand-foot-and-mouth disease (HFMD), enteroviral meningitis, and acute flaccid paralysis (AFP). The majority of EVA71 belonged to genotype C4, while a smaller percentage belonged to genotype B5. This highlights the importance of surveillance, outbreak prediction, and vaccination to combat EVA71-associated infections.
Article
Biochemistry & Molecular Biology
Pu Chen, Justyna Aleksandra Wojdyla, Ombretta Colasanti, Zhijian Li, Bo Qin, Meitian Wang, Volker Lohmann, Sheng Cui
Summary: This study identified a previously unfound activity of HAV 2C, which is a ribonuclease activity. The crystal structure of an HAV 2C fragment was determined, and the importance of the PBD-Pocket interaction for 2C functions was demonstrated. Furthermore, it was found that other picornavirus 2Cs also possess ribonuclease activity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Li-Fei Tian, Xiaolin Kuang, Ke Ding, Hongwei Gao, Qun Tang, Xiao-Xue Yan, Wenqing Xu
Summary: This study reveals the structure and function of the DNA repair protein RadD during the process of DNA damage repair. Key amino acids Gly34 and Gly36, as well as Lys37 and Arg343, in RadD are crucial for ATP binding and ATPase activity. Asp117 polarizes the attacking water molecule to form the transition state, while Lys68 regulates substrate entry and product release. Additionally, we found that the C-terminal peptide of single-stranded DNA-binding protein (SSB) enhances RadD's ATPase activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Tianrun Liu, Yingyu Li, Lumeng Wang, Xiaomeng Zhang, Yuxuan Zhang, Xuejie Gai, Li Chen, Lei Liu, Limin Yang, Baixin Wang
Summary: This study investigated the effects of mulberry leaf on enterovirus 71 (EV71) using network pharmacology, molecular docking, and in vitro experiments. The results revealed that quercetin, a major ingredient in mulberry leaf, exhibits potent anti-EV71 properties by inhibiting the NF-kappa B signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ammar M. Hassanbhai, Meng Chee Phoon, Vincent T. Chow, Bow Ho
Summary: This study investigates the interactions between enterovirus 71 (EV71) and the biofilm formed by Helicobacter pylori. The results show that the H. pylori biofilm can prolong the survival of EV71 and the quantity of biofilm formation affects the viability of the virus. This suggests that the H. pylori biofilm may serve as an additional pathway for EV71 transmission.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Chu Zhang, Fan Yang, Justyna Aleksandra Wojdyla, Bo Qin, Wei Zhang, Min Zheng, Weijun Cao, Meitian Wang, Xiaopan Gao, Haixue Zheng, Sheng Cui
Summary: The crystal structure of an FMDV 2C fragment reveals its similarity with enterovirus 2C protein. An anti-FMDV peptide derived from 2C protein disrupts its activity and shows anti-FMDV activity in cells.
Article
Multidisciplinary Sciences
Daniel L. Hurdiss, Priscila El Kazzi, Lisa Bauer, Nicolas Papageorgiou, Francois P. Ferron, Tim Donselaar, Arno L. W. van Vliet, Tatiana M. Shamorkina, Joost Snijder, Bruno Canard, Etienne Decroly, Andrea Brancale, Tzviya Zeev-Ben-Mordehai, Friedrich Forster, Frank J. M. van Kuppeveld, Bruno Coutard
Summary: This study reveals the crystal structure of the binding complex between enterovirus 2C protein and fluoxetine, uncovering an allosteric binding site. By engineering a hexameric form of 2C protein, the study demonstrates that compounds like fluoxetine can inhibit the ATPase activity of 2C. Cryo-electron microscopy analysis further shows how fluoxetine locks 2C protein in a hexameric state. These findings provide important insights into the inhibition mechanism of 2C and offer a robust engineering strategy for studying its structure, function, and drug-screening analysis.
Article
Chemistry, Applied
Xiaoxiang Gao, Yinghui Qiu, Luying Gao, Lizhu Zhang, Xiaoqing Li, Yuanyuan Liu, Chao Zhao
Summary: This study demonstrates that LNFPI can inhibit EV71 infection by reducing virus adsorption and promoting the expression of cyclin E, leading to virus-induced S phase arrest and apoptosis inhibition. Moreover, LNFPI can also regulate the abundance of intestinal flora to suppress cell apoptosis. These findings provide new recommendations for the supplementation of LNFPI in infant formula, offering antiviral benefits to formula-fed infants.
Article
Pharmacology & Pharmacy
Wen-Wan Chao, Yueh-Hsiung Kuo, Bi-Fong Lin
Summary: The study demonstrated that bioactive compounds from Andrographis paniculata and its derivatives have potential in protecting EV71-infected cells, inhibiting cell apoptosis, and promoting immune responses, suggesting that they may be feasible for the development of anti-EV71 agents.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Xiaopan Gao, Kaixiang Zhu, Justyna Wojdyla, Pu Chen, Bo Qin, Ziheng Li, Meitian Wang, Sheng Cui
Article
Chemistry, Multidisciplinary
Chia-Ying Huang, Nathalie Meier, Martin Caffrey, Meitian Wang, Vincent Olieric
JOURNAL OF APPLIED CRYSTALLOGRAPHY
(2020)
Article
Biochemistry & Molecular Biology
Wenting Bu, Zarina Levitskaya, Zhi Yang Loh, Shengyang Jin, Shibom Basu, Rya Ero, Xinfu Yan, Meitian Wang, So Fong Cam Ngan, Siu Kwan Sze, Suet-Mien Tan, Yong-Gui Gao
Article
Biochemical Research Methods
Greta M. Assmann, Meitian Wang, Kay Diederichs
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2020)
Article
Pharmacology & Pharmacy
Xiaopan Gao, Bo Qin, Pu Chen, Kaixiang Zhu, Pengjiao Hou, Justyna Aleksandra Wojdyla, Meitian Wang, Sheng Cui
Summary: This study provided structural frameworks for PLpro inhibitor design targeting SARS-CoV-2, showing that existing SARS-CoV PLpro inhibitors have some efficacy against SARS-CoV-2 and explored the inhibition mechanism of GRL0617.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Multidisciplinary Sciences
Wei Hao, Bo Ma, Ziheng Li, Xiaoyu Wang, Xiaopan Gao, Yaohao Li, Bo Qin, Shiying Shang, Sheng Cui, Zhongping Tan
Summary: The study found that the spike proteins and subunits of SARS-CoV-2, SARS-CoV, and MERS-CoV can bind to heparan sulfate (HS) in a sulfation-dependent manner, with no binding to sialic acid residues detected. This suggests that HS binding may be a general mechanism for these coronaviruses to attach to host cells.
Article
Multidisciplinary Sciences
Xiaopan Gao, Kaixiang Zhu, Bo Qin, Vincent Olieric, Meitian Wang, Sheng Cui
Summary: Orf9b, a unique accessory protein of SARS-CoV-2 and SARS-CoV, interacts with TOM70 to potentially interfere with immunity and suppress interferon responses by inhibiting the Hsp90/TOM70 interaction. The specific mechanisms of these interactions shed light on the pathogenesis of these coronaviruses.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Xiaopan Gao, Xia Yu, Kaixiang Zhu, Bo Qin, Wei Wang, Pu Han, Justyna Aleksandra Wojdyla, Meitian Wang, Sheng Cui
Summary: Mycobacterium tuberculosis (Mtb) caused approximately 10 million tuberculosis cases and 1.2 million deaths globally in 2019. The crystal structure of Mtb EF-G1 in complex with GDP provides a valuable platform for fragment-based screening and aids in the identification of potential EF-G1 inhibitors for drug discovery.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemical Research Methods
Jakub W. Kaminski, Laura Vera, Dennis P. Stegmann, Jonatan Vering, Deniz Eris, Kate M. L. Smith, Chia Ying Huang, Nathalie Meier, Julia Steuber, Meitian Wang, Guenter Fritz, Justyna A. Wojdyla, May E. Sharpe
Summary: Fragment-based drug discovery has been proven to be an effective and efficient method for identifying new chemical scaffolds. X-ray crystallography can be used to validate and develop identified fragments, and recent technological advancements have enabled the development of dedicated platforms for FBDD using X-ray crystallography.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pu Chen, Justyna Aleksandra Wojdyla, Ombretta Colasanti, Zhijian Li, Bo Qin, Meitian Wang, Volker Lohmann, Sheng Cui
Summary: This study identified a previously unfound activity of HAV 2C, which is a ribonuclease activity. The crystal structure of an HAV 2C fragment was determined, and the importance of the PBD-Pocket interaction for 2C functions was demonstrated. Furthermore, it was found that other picornavirus 2Cs also possess ribonuclease activity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Xiaopan Gao, Huabin Tian, Kaixiang Zhu, Qing Li, Wei Hao, Linyue Wang, Bo Qin, Hongyu Deng, Sheng Cui
Summary: This study reveals the molecular basis for the antagonistic function of Sarbecovirus ORF6 and suggests a potential strategy for immunosuppressive drug development using ORF6 CTT-derived peptides.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Pengjiao Hou, Wei Hao, Bo Qin, Mengyun Li, Rong Zhao, Sheng Cui
Summary: Schlafen11 is a well-studied protein that plays important roles in cancer therapy and virus-host interactions. The crystal structure and biochemical characteristics of the N-terminal domain (NTD) of Schlafen11 were determined, revealing its potent RNase activity towards type I and II tRNAs and rRNAs. These findings enhance our understanding of the Schlafen family.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Bo Qin, Ziheng Li, Kaiming Tang, Tongyun Wang, Yubin Xie, Sylvain Aumonier, Meitian Wang, Shuofeng Yuan, Sheng Cui
Summary: This study reveals that SARS-CoV-2 SUD has druggable sites for antiviral development and identifies theaflavin 3,3'-digallate as a potent SUD binder with anti-SARS-CoV-2 activity.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Shuofeng Yuan, Xiaopan Gao, Kaiming Tang, Jian-Piao Cai, Menglong Hu, Peng Luo, Lei Wen, Zi-Wei Ye, Cuiting Luo, Jessica Oi-Ling Tsang, Chris Chun-Yiu Chan, Yaoqiang Huang, Jianli Cao, Ronghui Liang, Zhenzhi Qin, Bo Qin, Feifei Yin, Hin Chu, Dong-Yan Jin, Ren Sun, Jasper Fuk-Woo Chan, Sheng Cui, Kwok-Yung Yuen
Summary: The study identifies a noncovalent lead inhibitor, F0213, with broad-spectrum antiviral activity against various coronaviruses, including SARS-CoV-2. The compound provides protection in animal models and exhibits dual therapeutic functionality by inhibiting viral polyprotein cleavage and promoting antiviral immunity. The mode of inhibition differs between SARS2-PLpro and MERS-PLpro. These findings suggest that targeting the papain-like protease domain could be a potential strategy for developing pan-coronaviral therapeutics.