Article
Microbiology
Hye-Jin Shin, Mi-Hwa Kim, Joo-Youn Lee, Insu Hwang, Gun-Young Yoon, Hae-Soo Kim, Young-Chan Kwon, Dae-Gyun Ahn, Kyun-Do Kim, Bum-Tae Kim, Seong-Jun Kim, Chonsaeng Kim
Summary: The Zika virus and dengue virus are closely related and may exacerbate disease when circulating together. A potential drug has been discovered to effectively inhibit the infection of both viruses, showing promise for the development of more potent antiviral drugs.
Article
Pharmacology & Pharmacy
Muhammad Usman Mirza, Ida Alanko, Michiel Vanmeert, Kendall M. Muzzarelli, Outi M. H. Salo-Ahen, Iskandar Abdullah, Iulia A. Kovari, Sandra Claes, Steven De Jonghe, Dominique Schols, Raymond F. Schinazi, Ladislau C. Kovari, John F. Trant, Sarfraz Ahmad, Matheus Froeyen
Summary: This study used a computer-aided structure-based approach to screen a library of compounds against ZIKV NS2B-NS3 protease. Several compounds showed promising activity against the protease, and one compound also exhibited anti-ZIKV activity in whole cells. This research provides a promising starting point for the development of novel compounds against ZIKV.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fadi G. Saqallah, Manal A. Abbas, Habibah A. Wahab
Summary: Dengue virus is a mosquito-borne virus that can cause various complications. A tetravalent vaccine is available for children, and the NS2b/NS3 protease is a key target for antiviral agents. Natural products have shown potential as inhibitors of dengue virus, with some compounds found to inhibit the NS2b/NS3 protease. However, further in vivo and clinical studies are needed.
Article
Pharmacology & Pharmacy
Juan Miao, Honggen Yuan, Jingwei Rao, Jiahui Zou, Kelu Yang, Guiqing Peng, Shengbo Cao, Huanchun Chen, Yunfeng Song
Summary: A compound with high and specific inhibitory effects on ZIKV NS2B-NS3 protease has been identified in this study. The compound showed antiviral effects and protection in cell and mouse models, making it a potential therapeutic agent.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Mahesh Samantaray, Ramya Pattabiraman, T. P. Krishna Murthy, Amutha Ramaswamy, Manikanta Murahari, Swati Krishna, S. Birendra Kumar
Summary: In this study, a structure-based drug design approach was used to screen a large library of natural compounds against the NS3-4A protease of Hepatitis C Virus. Molecular dynamic simulations and Free Energy Landscape analysis showed that certain compounds had favorable binding affinities and formed stable associations with the target protease through hydrogen bonding. These compounds have the potential to be further validated through biological evaluation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Yanchao Xiong, Fei Cheng, Junyi Zhang, Haixia Su, Hangchen Hu, Yi Zou, Minjun Li, Yechun Xu
Summary: This study reveals the structure and ligand-binding mode of the Zika virus NS2B/NS3 protease through crystallography and experimental results. A novel inhibitor with higher potency and efficiency than existing drugs is designed based on the detailed binding modes of two ligands. These findings provide valuable clues for the development of more potent inhibitors of the Zika virus NS2B/NS3 protease.
BIOORGANIC CHEMISTRY
(2022)
Review
Virology
Hui-Chun Li, Chee-Hing Yang, Shih-Yen Lo
Summary: The life cycle of the hepatitis C virus can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and release. The replication of HCV genomic RNA is regulated by various factors and has led to the development of direct-acting antivirals targeting the replication complex.
Article
Pharmacology & Pharmacy
Zhong Li, Jimin Xu, Yuekun Lang, Xiangmeng Wu, Saiyang Hu, Subodh Kumar Samrat, Anil M. Tharappel, Lili Kuo, David Butler, Yongcheng Song, Qing-Yu Zhang, Jia Zhou, Hongmin Li
Summary: Erythrosin B is an effective antiviral against Zika virus both in vitro and in vivo, and its derivatives are non-toxic to human cells.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Multidisciplinary Sciences
Omar Cruz-Arreola, Abdu Orduna-Diaz, Fabiola Dominguez, Julio Reyes-Leyva, Veronica Vallejo-Ruiz, Lenin Dominguez-Ramirez, Gerardo Santos-Lopez
Summary: This study explored the potential targets for treating dengue and Zika viruses by analyzing the binding affinity of certain molecules found in medicinal plants to NS3-helicase and NS3-protease. The results suggest that quercetin derivatives could block the activity of NS3-protease in both viruses. A new molecule called MOD10 was designed and showed improved interaction and trajectory compared to the original molecules. These findings provide new insights for the development of antiviral treatments against dengue and Zika viruses.
Article
Biochemistry & Molecular Biology
See Khai Lim, Rozana Othman, Rohana Yusof, Choon Han Heh
Summary: This study aimed to discover novel benzopyran-based inhibitors targeting the NS3 enzymes of HCV G3 using structure-based virtual screening and in vitro approaches. Six novel compounds were found to inhibit HCV G3 NS3/4A protease, and two phytochemicals were identified as dual-target inhibitors. In cell-based assays, some compounds showed dose-dependent inhibition against HCV G3 replicons.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Pharmacology & Pharmacy
Juliana Cotabarren, Santiago Claver, Juan Abreu Payrol, Javier Garcia-Pardo, Walter David Obregon
Summary: In this study, the first phytocystatin MoPI isolated from Moringa oleifera was characterized for its potent inhibitory activity against cysteine proteases, antimicrobial activity against human pathogens, and anticoagulant activity. These findings highlight the pharmaceutical potential of this plant and its bioactive molecules.
Article
Biochemistry & Molecular Biology
Thitiya Boonma, Bodee Nutho, Nitchakan Darai, Thanyada Rungrotmongkol, Nadtanet Nunthaboot
Summary: A156T mutation in HCV NS3/4A serine protease leads to drug resistance, and the newly approved drugs paritaprevir and glecaprevir exhibit different resistance profiles against this mutation. Molecular dynamics simulations and binding free energy calculations reveal that the binding affinities of paritaprevir and glecaprevir to A156T NS3/4A are significantly reduced compared to their wild-type complexes. The main contributions for the higher resistance of glecaprevir are the weak interactions with specific amino acids in NS3 protein and destabilized protein binding surface.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Simon Huber, Niklas J. Braun, Luna C. Schmacke, Jun Ping Quek, Robin Murra, Daniela Bender, Eberhard Hildt, Dahai Luo, Andreas Heine, Torsten Steinmetzer
Summary: A series of new macrocyclic inhibitors of the Zika virus protease have been synthesized, with some exhibiting high inhibitory activity. One inhibitor showed antiviral effect, along with excellent selectivity profile and low cytotoxicity. These findings provide valuable information for the development of drugs against Zika virus and related flaviviruses.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sakshi Kamboj, Akanksha Rajput, Amber Rastogi, Anamika Thakur, Manoj Kumar
Summary: This study developed the Anti-HCV platform using machine learning and QSAR approaches to predict repurposed drugs targeting HCV non-structural proteins. Different machine learning techniques were used to develop predictive models, which were validated through molecular docking. Promising repurposed drugs were identified, which may be useful in antiviral drug development against HCV.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Medicine, Research & Experimental
Zsofia Gabriella Pesei, Zsanett Jancso, Alexandra Demcsak, Balazs Csaba Nemeth, Sandor Vajda, Miklos Sahin-Toth
Summary: This study demonstrates that dabigatran etexilate can inhibit pancreatic trypsins and effectively treat trypsin-dependent pancreatitis, providing a proof of concept. The drug competitively inhibits all human and mouse trypsin isoforms and shows therapeutic activity in mouse models.