Article
Microbiology
Chih-Hung Chuang, Tian-Lu Cheng, Wei-Chun Chen, Yi-Jung Huang, Hsin-Ell Wang, Yen-Chen Lo, Yuan-Chin Hsieh, Wen-Wei Lin, Ya-Ju Hsieh, Chien-Chih Ke, Kang-Chieh Huang, Jin-Ching Lee, Ming-Yii Huang
Summary: The study developed a protease-activatable retention probe for tracking the activity of hepatitis C virus NS3/4A protease. This probe can be detected using positron emission topography (PET) imaging to monitor the distribution and activity of NS3/4A protease.
FRONTIERS IN MICROBIOLOGY
(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)
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
Virology
Fengwei Zheng, Weicheng Yi, Weichi Liu, Hongchang Zhu, Peng Gong, Zishu Pan
Summary: The study explored the relationship between a positively charged patch on the protease module and NS3 function through biochemical and genetic approaches. The results indicated that mutations in the conserved positively charged patch on NS3 affected the helicase activity and RNA-binding ability of NS3, and impaired the production of infectious virus in classical swine fever virus (CSFV) invitro. The replication efficiency of the CSFV variants was partially correlated with the helicase activity of NS3.
ARCHIVES OF VIROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Asmaa Abo Elgoud Said, Ahmed H. Afifi, Taha F. S. Ali, Mamdouh Nabil Samy, Usama Ramadan Abdelmohsen, Mostafa A. Fouad, Eman Zekry Attia
Summary: Chemical investigation of Aptenia cordifolia roots extract resulted in isolation and identification of eight known compounds. The basic ethyl acetate fraction showed high activity against HCV with an IC50 value of 2.4 mu g mL(-1), and some compounds exhibited strong binding to the active site of NS3/4A helicase.
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
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
Virology
Tadahisa Teramoto
Summary: Enzyme activities for replicating DENV 5' cap positive (+) sense RNA have been shown to reside in NS3 and NS5. However, it remains unknown how these enzymes coordinately synthesize negative (-) sense RNA, from which abundant 5' cap (+) sense RNA is produced. We previously revealed that NS5 dimerization and NS5 methyltransferase(MT)-NS3HEL interaction are important for DENV replication. Here, we found that replication incompetence due to NS3PRO or HEL replacement was compensated by a mutation at HEL or NS2B, respectively, suggesting that the interactions among NS2B, NS3PRO, and HEL are critical for DENV replication.
JOURNAL OF VIROLOGY
(2023)
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
Chemistry, Physical
Chen-Ji Huang, Hwei-Ling Peng, Anil Kumar Patel, Reeta Rani Singhania, Cheng-Di Dong, Chih-Yu Cheng
Summary: By designing a truncated NS3 protein, the expression and purification in E. coli were successfully improved, with fresh NS3 demonstrating higher specificity and antigenic activity. Long-term storage and thermal stability studies further confirmed the potential application value of fresh NS3 in HCV ELISA diagnosis.
Article
Biochemistry & Molecular Biology
Caiying Zhang, Yuelong Li, Abdus Samad, Hongliang He, Huan Ma, Yang Chen, Tengchuan Jin
Summary: The KFDV NS3 helicase is a potential drug target involved in viral replication complex, and its ATPase activity is enhanced by dsRNA and inhibited by DNA. Several key residues for its ATPase activity were identified through mutagenesis analysis. The tea-derived polyphenol EGCG strongly inhibited NS3hel ATPase activity and bound to predicted druggable hotspots of NS3hel.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Biochemistry & Molecular Biology
Vishal S. Patil, Darasaguppe R. Harish, Umashankar Vetrivel, Subarna Roy, Sanjay H. Deshpande, Harsha V. Hegde
Summary: This study investigates the interactions of phytochemicals from Terminalia chebula with HCV and human proteins using network pharmacology and structural bioinformatics techniques. The results show that chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose have potent inhibitory activity against HCV NS3/4A and can potentially modulate the host immune system. These findings suggest that tannins from T. chebula could be potential drugs for the treatment of HCV and immune-related diseases.
Article
Chemistry, Medicinal
Desaboini Nageswara Rao, Jacqueto Zephyr, Mina Henes, Elise T. Chan, Ashley N. Matthew, Adam K. Hedger, Hasahn L. Conway, Mohsan Saeed, Alicia Newton, Christos J. Petropoulos, Wei Huang, Nese Kurt Yilmaz, Celia A. Schiffer, Akbar Ali
Summary: By designing and synthesizing compounds with different chemical scaffolds at the P2 and P4 positions, researchers developed pan-genotypic HCV NS3/4A protease inhibitors with excellent antiviral activity and improved drug resistance profiles.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Gastroenterology & Hepatology
Margaret E. Hellard, Alisa Pedrana
Summary: Collaborating with local community organizations and using a pay-it-forward approach, Zhang et al. successfully increased hepatitis B and hepatitis C testing among men who have sex with men in China.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Chemistry, Multidisciplinary
T. Ghiasi, S. Ahmadi, E. Ahmadi, M. R. Talei Bavil Olyai, Z. Khodadadi
Summary: Robust QSAR models were developed using CORAL software to predict IC50 values of hepatitis C virus NS3/4A protease inhibitors, with models based on TF2 statistically more significant and reliable than those based on TF1.
SAR AND QSAR IN ENVIRONMENTAL RESEARCH
(2021)