Article
Chemistry, Multidisciplinary
Asmat Ullah, Atia-tul-Wahab, Peng Gong, Abdul Mateen Khan, M. Iqbal Choudhary
Summary: The rapid spread of dengue virus is a major health problem worldwide. This study evaluated 75 compounds for their ability to interact with NS5 protein and identified 12 potential antiviral agents against dengue virus.
Article
Virology
Xuejian Du, Zeng-Qiang Gao, Zhi Geng, Yu-Hui Dong, Heng Zhang
Summary: ASFV protein pNP868R with GTase activity plays a crucial role in mRNA capping process.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Priscilla L. S. Boon, Ana S. Martins, Xin Ni Lim, Francisco J. Enguita, Nuno C. Santos, Peter J. Bond, Yue Wan, Ivo C. Martins, Roland G. Huber
Summary: Dengue virus is a significant health risk in tropical and subtropical regions. The structure of the packaged genome in complex with C proteins remains elusive. This study investigates the interactions of C proteins with viral RNA and shows their role in coordinating key interactions for proper packaging of viral RNA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Gopinathan Pillai Sreekanth
Summary: Dengue virus infection is a significant arboviral infection in humans. Non-structural protein 5 (DENV-NS5) of DENV consists of two domains, RdRp and MTase, which play important roles in viral replication. Targeting DENV-NS5 could be a potential therapeutic strategy for dengue virus infection.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Philipe O. Fernandes, Marcelo A. Chagas, Willian R. Rocha, Adolfo H. Moraes
Summary: NS5 protein plays a crucial role in flavivirus replication and is a promising drug target; most NS5 inhibitor candidates target active sites, but similarity with human enzymes may lead to side effects; identifying new allosteric sites in NS5 could greatly contribute to antiviral development.
CURRENT OPINION IN VIROLOGY
(2021)
Article
Biochemical Research Methods
Vivek Dhar Dwivedi, Aditya Arya, Pardeep Yadav, Rajesh Kumar, Vinod Kumar, Gajendra P. S. Raghava
Summary: The DenvinD database provides comprehensive information on experimentally validated DENV inhibitors against known targets, and offers user-friendly web-based features for simple search, advanced search, and data browsing. This database is the first useful repository of its kind, aiding in advancing DENV drug discovery research.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biology
Takuo Minato, Takamasa Teramoto, Naruhiko Adachi, Nguyen Khac Hung, Kaho Yamada, Masato Kawasaki, Masato Akutsu, Toshio Moriya, Toshiya Senda, Seiji Ogo, Yoshimitsu Kakuta, Ki-Seok Yoon
Summary: Takuo Minato and colleagues have identified both a conventional hexameric structure and a novel octameric structure in native C-phycocyanin (CPC) from the thermophilic cyanobacterium Thermoleptolyngbya sp. O77. The observation of an unusual dimeric state via analytical ultracentrifugation suggests a key intermediate structure in the assembly of octameric CPC. These findings offer new insights into the assembly processes of CPCs and the mechanism of energy transfer in light-harvesting complexes.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biology
Krishan K. Pandey, Sibes Bera, Ke Shi, Michael J. Rau, Amarachi V. Oleru, James A. J. Fitzpatrick, Alan N. Engelman, Hideki Aihara, Duane P. Grandgenett
Summary: Pandey, Bera, Shi et al. reported the cryo-electron microscopy structure of the Rous sarcoma virus octameric intasome complex stabilized by a HIV-1 integrase strand transfer inhibitor. This new structure highlighted the intrinsic flexibility of the distal integrase subunits and proposed ordered conformational transitions within the conserved intasome core during the assembly process.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marcelo Chagas, Willian Rocha, Adolfo Moraes
Summary: MTase domain of NS5 protein in flaviviruses plays a fundamental role in viral replication and its inhibition is a strategy for antiviral development. The dynamic changes related to ligand binding and methyl transfer reaction were investigated by studying the structural dynamics of ZIKV NS5 MTase domain free and bound to GTP and SAM. The binding of GTP and SAM induced allostery in the RNA binding site, showing the complexity of MTase conformational equilibrium and its impact on viral RNA recognition.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Virology
Hemalatha Beesetti, Sathyamangalam Swaminathan
Summary: In this study, a HuAd5 vector encoding shRNA was shown to effectively suppress the replication of all four prototypic DENV serotypes in Vero cells and human macrophages. The HuAd5 vector-mediated DENV suppression in macrophages was found to be dependent on the presence of anti-HuAd5 antibodies, suggesting implications for the specific targeting of HuAd5 vector-mediated antiviral RNA interference therapy to macrophages.
Article
Virology
Jennifer S. H. Im, Jasmine R. Sheppard, K. Andrew White
Summary: Red clover necrotic mosaic virus (RCNMV) is a segmented positive-strand RNA virus consisting of RNA1 and RNA2. Efficient translation of RCNMV RNA2 requires de novo synthesis of RNA2 during infections, and its replication is necessary for translation. The 5' untranslated region (5' UTR) of RNA2 contains structural elements that can adopt alternative conformations to regulate translation and replication. The alternative conformation with unpaired 5'-terminal nucleotides mediates efficient translation, while the more stable 5'-basal stem structure (5' BS) suppresses translation and confers stability to RNA2.
Article
Microbiology
Mayra Diosa-Toro, Debbie R. Kennedy, Vanessa Chuo, Vsevolod L. Popov, Julien Pompon, Mariano A. Garcia-Blanco
Summary: Infection with dengue virus induces rearrangements of the endoplasmic reticulum, and a host RNA-binding protein YBX1 plays a crucial role in viral replication and assembly by interacting with the viral nucleocapsid and participating in assembly sites.
Article
Microbiology
Mayra Diosa-Toro, Debbie R. Kennedy, Vanessa Chuo, Vsevolod L. Popov, Julien Pompon, Mariano A. Garcia-Blanco
Summary: Y-box binding protein 1 (YBX1) interacts with the viral nucleocapsid, distributes to DENV assembly sites, and is necessary for efficient assembly of intracellular infectious virions.
Article
Multidisciplinary Sciences
Meng Liu, Gangqiang Guo, Pengge Qian, Jianbing Mu, Binbin Lu, Xiaoqin He, Yanting Fan, Xiaomin Shang, Guang Yang, Shijun Shen, Wenju Liu, Liping Wang, Liang Gu, Quankai Mu, Xinyu Yu, Yuemeng Zhao, Richard Culleton, Jun Cao, Lubin Jiang, Thomas E. Wellems, Jing Yuan, Cizhong Jiang, Qingfeng Zhang
Summary: m5C modification is an important regulator of mRNA stability and translation efficiency in malaria parasites. This study characterized the landscape of m5C mRNA modifications in different developmental stages of rodent and human malaria parasites. The results showed that m5C modifications confer stability to Plasmodium transcripts and that NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Knockout of the nsun2 gene resulted in reduced m5C modification and impaired gametocyte production, which was rescued by restoration of the nsun2 gene. These findings highlight the significant role of NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
De-Ping Wang, Rong Zhao, Hao-Feng Wang, Mei-Yue Wang, Wen-Shu Hu, Meng -Meng Lin, Wen Shu, Yao-Jun Sun, Ji-Min Cao, Wen Cui, Xin Zhou
Summary: This study provides insights into the development of potential anti-monkeypox drugs by analyzing the crystal structure of a key enzyme in the replication of the monkeypox virus and identifying potential inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Bing Liang Alvin Chew, Frederick Reinhart Tanoto, Dahai Luo
Article
Pharmacology & Pharmacy
Wint Wint Phoo, Abbas El Sahili, ZhenZhen Zhang, Ming Wei Chen, Chong Wai Liew, Julien Lescar, Subhash G. Vasudevan, Dahai Luo
ANTIVIRAL RESEARCH
(2020)
Article
Cell Biology
Stephanie A. Moquin, Oliver Simon, Ratna Karuna, Suresh B. Lakshminarayana, Fumiaki Yokokawa, Feng Wang, Chandra Saravanan, Jin Zhang, Craig W. Day, Katherine Chan, Qing-Yin Wang, Siyan Lu, Hongping Dong, Kah Fei Wan, Siew Pheng Lim, Wei Liu, Cheah Chen Seh, Yen-Liang Chen, Haoying Xu, David T. Barkan, Cyrille S. Kounde, Wei Lin Sandra Sim, Gang Wang, Hui-Quan Yeo, Bin Zou, Wai Ling Chan, Mei Ding, Jae-Geun Song, Min Li, Colin Osborne, Francesca Blasco, Christopher Sarko, David Beer, Ghislain M. C. Bonamy, Vito G. Sasseville, Pei-Yong Shi, Thierry T. Diagana, Bryan K. S. Yeung, Feng Gu
Summary: A potential chemical inhibitor, NITD-688, showed strong potency against all four serotypes of DENV and demonstrated excellent oral efficacy in mice, indicating it may be a promising preclinical candidate for dengue treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Kuohan Li, Jie Zheng, Melissa Wirawan, Nguyen Mai Trinh, Olga Fedorova, Patrick R. Griffin, Anna M. Pyle, Dahai Luo
Summary: DRH-3 plays a critical role in endogenous RNAi pathways, with its NTD structurally similar to CARDs of RLRs and CTD recognizing typical secondary siRNA transcripts. The unique structural dynamics of full-length DRH-3 upon binding to RNA duplexes differ from RIG-I or MDA5, showcasing the evolutionary divergence of Dicer and RLR family of helicases.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Medicinal
Crystall Swarbrick, Vasiliki Zogali, Kitti Wing Ki Chan, Dimitrios Kiousis, Chin Piaw Gwee, Sai Wang, Julien Lescar, Dahai Luo, Mark von Itzstein, Minos-Timotheos Matsoukas, George Panagiotakopoulos, Subhash G. Vasudevan, Gerasimos Rassias
Summary: The study presents a novel dengue protease inhibitor, SP-471, with high antiviral activity and no cellular toxicity, making it a promising candidate for dengue fever treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yaw Bia Tan, Laura Sandra Lello, Xin Liu, Yee-Song Law, Congbao Kang, Julien Lescar, Jie Zheng, Andres Merits, Dahai Luo
Summary: Alphaviruses are mosquito-borne pathogens that can cause arthritis or encephalitis. The nonstructural protein 4 (nsP4) of alphaviruses plays a crucial role in viral RNA replication. The crystal structures of the RdRp domain of nsP4 from Ross River virus and Sindbis virus were determined and found to be closely related to RdRps from other viruses. Understanding the structure and function of nsP4 is important for developing antiviral drugs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Sai Wang, Kitti Wing Ki Chan, Min Jie Alvin Tan, Charlotte Flory, Dahai Luo, Julian Lescar, Jade K. Forwood, Subhash G. Vasudevan
Summary: This study reveals the interaction between the nonstructural protein NS5 and the stem-loop A (SLA) in the 5' UTR, as well as the top-loop of 3' SL in the 3' UTR during flavivirus RNA replication. The conserved arginine 888 of DENV2 NS5 plays a crucial role in virus viability and de novo initiation of RNA polymerase activity.
Article
Biochemistry & Molecular Biology
Yixuan Lei, Panyu Fei, Bin Song, Wenjia Shi, Cheng Luo, Dahai Luo, Dan Li, Wei Chen, Jie Zheng
Summary: This study investigated how subtle conformational changes in the helicase insertion domain (HEL2i) of RIG-I can impair ATPase and RNA proofreading activities, leading to increased immunopathy. The findings highlight the importance of HEL2i as a checkpoint in controlling antiviral innate immunity and autoimmune diseases.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ezekiel Ze Ken Cheong, Jun Ping Quek, Liu Xin, Chaoqiang Li, Jing Yi Chan, Chong Wai Liew, Yuguang Mu, Jie Zheng, Dahai Luo
Summary: This study reports a novel crystal structure of RubPro and investigates its functions. It was found that RubPro has protease and deubiquitylation activities, potentially modulating the host's immune responses. These structural and functional insights advance our understanding of RUBV replication and may facilitate the development of antiviral therapeutics.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Phuong Thao Ly, Shaohai Xu, Melissa Wirawan, Dahai Luo, Xavier Roca
Summary: The study demonstrates that different isoforms of ZAP play overlapping yet different roles in antiviral defense and other cellular processes. The regulation of host mRNA by ZAP is mostly unknown, but splice-switching antisense oligonucleotides can modulate the balance between ZAP isoforms. The study also identifies new cellular transcripts and processes regulated by ZAP isoforms, such as unfolded protein response, epithelial-mesenchymal transition, and innate immunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Siew Pheng Lim
Summary: Despite the availability of vaccines and therapeutics, continuous genetic alterations in the SARS-CoV-2 virus pose a persistent threat, especially to immunocompromised and elderly individuals. The virus enters host cells via the interaction of its spike protein (S protein) with different receptors on the cell surface, such as angiotensin-converting enzyme 2 (ACE2). This review discusses therapeutic approaches to block the interaction between SARS-CoV-2 and host cell receptors, as well as the identification of auxiliary entry receptors.
ANTIVIRAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Yaw Bia Tan, Michelle Cheok Yien Law, Dahai Luo
Summary: This article discusses the assembly and function of the virus RC, and highlights its potential as a multi-enzyme target for developing antiviral drugs. It also suggests that the alphavirus RC has therapeutic potential through self-amplifying RNA technology for both infectious and non-infectious diseases.
ANTIVIRAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Yaw Bia Tan, David Chmielewski, Michelle Cheok Yien Law, Kuo Zhang, Yu He, Muyuan Chen, Jing Jin, Dahai Luo
Summary: This study reveals the high-resolution structure of the core RNA replicase of chikungunya virus and the native RC architecture in its cellular context using in vitro reconstitution and in situ electron cryotomography. The viral polymerase nsP4, in complex with nsP2 helicase-protease, is located in the central pore of the membrane-anchored nsP1 RNA-capping ring within the core RNA replicase. Additionally, a large cytoplasmic ring is found next to the C terminus of nsP1, forming the holo-RNA-RC at the neck of spherules formed in virus-infected cells.
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
Multidisciplinary Sciences
Geraldine Goh, Matae Ahn, Feng Zhu, Lim Beng Lee, Dahai Luo, Aaron T. Irving, Lin-Fa Wang
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)