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
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
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
Gastroenterology & Hepatology
Tetsuo Takehara, Namiki Izumi, Satoshi Mochida, Takuya Genda, Shigetoshi Fujiyama, Kazuo Notsumata, Akihiro Tamori, Fumitaka Suzuki, Vithika Suri, Renee-Claude Mercier, Takuma Matsuda, Kana Matsuda, Naoya Kato, Kazuaki Chayama, Hiromitsu Kumada
Summary: This study examined the efficacy and safety of sofosbuvir-velpatasvir in Japanese patients with HCV and compensated cirrhosis. The results showed that all participants achieved sustained virologic response 12 weeks after treatment, with no treatment breakthrough or relapse. This treatment regimen was safe and well tolerated.
HEPATOLOGY RESEARCH
(2022)
Article
Medicine, General & Internal
Mohammad Asrar Izhari
Summary: This study aimed to determine the increasing risk of direct-acting antiviral (DAA) resistance due to amino acid substitutions in non-structural proteins of the hepatitis C virus (HCV). Through sequence analysis, the study identified several resistance-associated amino acid substitutions in DAA target proteins. The findings highlight the importance of continuous monitoring and evaluation of DAA resistance in the treatment of HCV.
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)
Review
Health Care Sciences & Services
JiHyun An, Dong Ah Park, Min Jung Ko, Sang Bong Ahn, Jeong-Ju Yoo, Dae Won Jun, Sun Young Yim
Summary: DAA therapy has shown safety and efficacy in patients with decompensated cirrhosis. The SVR rate was 86%, with low rates of HCC occurrence and mortality. PI-based treatment demonstrated similar clinical outcomes and adverse events compared to non-PI-based DAA treatment in DC patients.
JOURNAL OF PERSONALIZED MEDICINE
(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
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.
Article
Chemistry, Medicinal
Shenyou Nie, Jidong Zhao, Xiaowei Wu, Yuan Yao, Fangrui Wu, Yi-Lun Lin, Xin Li, Alexander R. Kneubehl, Megan B. Vogt, Rebecca Rico-Hesse, Yongcheng Song
Summary: A novel series of compounds have been discovered as potent inhibitors of the Zika virus protease, with the most effective ones also showing inhibitory effects on dengue and West Nile virus. The most potent compounds were able to strongly inhibit Zika virus replication in cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
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
Tanaya Bagga, Nikhil Kumar Tulsian, Yu Keung Mok, R. Manjunatha Kini, J. Sivaraman
Summary: This study reveals the interaction and ubiquitination process between TRIM69 and Dengue NS2B-NS3 Delta pro, and identifies the conservation of TRIM69 targeting regions across various flaviviruses.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
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
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
Virology
Xiaoying Jia, Jiao Guo, Weirong Yuan, Lingling Sun, Yang Liu, Minmin Zhou, Gengfu Xiao, Wuyuan Lu, Alfredo Garzino-Demo, Wei Wang
Summary: The study showed that RC-101 can inhibit flavivirus infection and has potential therapeutic effects. The drug acts on both the entry and replication stages of the virus, potentially disrupting the activity of the nonstructural protein and the binding of the viral protein.
JOURNAL OF VIROLOGY
(2021)