Article
Chemistry, Physical
Sanghoon Shin, Yuhyun Kim, Sungwoo Hong
Summary: In this study, an innovative Ag(I)-catalyzed carbene transfer reaction using [1.1.1]propellane as a precursor was reported. The method involves the formation of Ag-bound oxonium ions as intermediates through the reaction between the Ag-carbene complex and cyclic ether-type solvents. The subsequent nucleophile-induced C-O bond cleavage leads to a controllable three-component etherification of methylene cyclobutane. The method demonstrates potential for the late-stage functionalization of complex, biologically relevant molecules and synthetic manipulations of the resulting products.
Article
Chemistry, Medicinal
Zhilan Zhou, Jifa Zhang, Enda Zhou, Changyu Ren, Jiaxing Wang, Yuxi Wang
Summary: HCV infection is a global health problem, and developing small-molecule inhibitors targeting NS5B RdRp is of great value. Non-nucleoside inhibitors have more flexible structures and simpler mechanisms compared to nucleoside inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Tomasz. M. Karpinski, Marcin Ozarowski, Pedro. J. Silva, Mark Stasiewicz, Rahat Alam, Abdus Samad
Summary: This study aimed to test the in silico activity of 1893 terpenes against HCV NS5B polymerase. Nine terpenes were identified as potential effective competitive inhibitors, forming stable interactions with the active site region.
Article
Microbiology
Rosario Sabariegos, Laura Albentosa-Gonzalez, Blanca Palmero, Pilar Clemente-Casares, Eugenio Ramirez, Carlos Garcia-Crespo, Isabel Gallego, Ana Isabel de avila, Celia Perales, Esteban Domingo, Antonio Mas
Summary: This study identified specific amino acids of the NS5B protein phosphorylated by cellular kinases, which may affect HCV RNA polymerase activity and lead to viral inactivation. Results from RNA transfection experiments with mutant viruses showed that T53E/A and S282E/A mutations had an impact on viral titers.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Virology
Tamer Nasr, Ahmed M. Aboshanab, George Mpekoulis, Antonios Drakopoulos, Niki Vassilaki, Grigoris Zoidis, Khaled A. M. Abouzid, Wafaa Zaghary
Summary: In this study, a novel series of 1-substituted phenyl-4(1H)-quinazolinone and 2-methyl-1-substituted phenyl-4(1H)-quinazolinone derivatives were synthesized and their activity against HCV was evaluated in HCV subgenomic replicon assays. Compound 11a and 11b showed promising activity and selectivity, making them potential candidates for the development of anti-HCV agents.
Article
Biochemical Research Methods
Hina Khalid, Usman Ali Ashfaq
Summary: This study utilized a computational approach to screen phytochemicals with potential NS5B polymerase inhibition against Hepatitis C Virus. The top-ranked compounds showed a promising binding affinity and favorable safety profile, indicating their potential as antiviral compounds against HCV.
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
(2022)
Article
Biochemistry & Molecular Biology
Qing Zhou, Yuhao Yang, Zhanxue Xu, Kai Deng, Zhenzhen Zhang, Jiawei Hao, Ni Li, Yanling Wang, Ziwen Wang, Haihang Chen, Yang Yang, Fei Xiao, Xiaohong Zhang, Song Gao, Yi-Ping Li
Summary: ATAD1 plays a crucial role in maintaining mitochondrial homeostasis and combating viral infection. HCV infection induces mitochondrial fragmentation and enhances the pro-infection effect of ATAD1 knockout. ATAD1 interacts with HCV NS5B protein and promotes its degradation, thereby exerting its antiviral function.
Article
Biochemical Research Methods
Heena Tarannum, Sisir Nandi
Summary: This study utilized structure-based molecular docking to repurpose RNA-dependent RNA polymerase inhibitors from dengue virus, yellow fever virus, and Zika virus for the treatment of hepatitis C virus (HCV). Several compounds were identified as potential leads for further testing and repurposing to combat HCV.
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
(2022)
Article
Biology
Laila K. Elghoneimy, Muhammad I. Ismail, Frank M. Boeckler, Hassan M. E. Azzazy, Tamer M. Ibrahim
Summary: This study conducted in-silico analysis to propose potential SARS CoV-2 RdRp palm subdomain binders as a remedy for COVID-19. By utilizing a high-quality custom-made DEKOIS 2.0 benchmark set, successful virtual screening was performed, recommending several potential binders.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Immunology
Pierre Cappy, Quentin Lucas, Nakourogou Kankarafou, Camille Sureau, Syria Laperche
Summary: Following a study demonstrating the role of hepatitis C virus (HCV) in transmitting hepatitis D virus (HDV) in a liver-humanized mouse model, a large cohort of HCV-positive blood donors were screened for HDV markers. However, no evidence of HCV-assisted propagation of HDV in humans was found.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Nils Frank, Jeremy Nugent, Bethany R. Shire, Helena D. Pickford, Patrick Rabe, Alistair J. Sterling, Tryfon Zarganes-Tzitzikas, Thomas Grimes, Amber L. Thompson, Russell C. Smith, Christopher J. Schofield, Paul E. Brennan, Fernanda Duarte, Edward A. Anderson
Summary: Small-ring cage hydrocarbons are popular bioisosteres for para-substituted benzene rings in drug design. In this study, we synthesized hydrocarbons called bicyclo[3.1.1]heptanes (BCHeps) from [3.1.1]propellane, which have geometric correspondence to meta-substituted benzenes. The BCHeps can be easily transformed into medicinally relevant carbon- and heteroatom-substituted compounds, displaying enhanced metabolic stability compared to their parent arene-containing drugs. This research demonstrates the potential of BCHeps as sp(3)-rich motifs in drug design and provides a new surrogate for meta-substituted benzene rings in drug discovery programs.
Article
Biochemistry & Molecular Biology
Di Han, Huiqun Wang, Baerlike Wujieti, Beibei Zhang, Wei Cui, Bo-Zhen Chen
Summary: This study elucidates the resistance mechanisms of GS-9669 caused by mutations in the NS5B polymerase of HCV, showing that these mutations reduce the binding affinity and can lead to different degrees of resistance. The results provide valuable insights for further optimization and design of novel NS5B inhibitors.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Chemistry, Analytical
Vigneswaran Narayanamurthy, Z. E. Jeroish, K. S. Bhuvaneshwari, Fahmi Samsuri
Summary: Proper diagnosis is essential in avoiding disease consequences, especially for severe issues like hepatitis C virus (HCV) that can cause significant damage to the liver. Developing strategies for appropriate selection of POCT for HCV detection, initiating proper antiviral therapy, and defining associated risks is critical for achieving optimal outcomes. Alternative strategies are needed to enhance HCV diagnosis, with molecular assays being precise but requiring additional approaches for infected populations to improve detection.
ANALYTICAL METHODS
(2021)
Article
Gastroenterology & Hepatology
Vanessa Koo, Feng Tian, William W. L. Wong
Summary: HCV point-of-care testing is cost-effective for injection drug users, as it can prolong individuals' lifespan and save healthcare costs associated with HCV-related complications.
LIVER INTERNATIONAL
(2022)
Article
Microbiology
Hyunyoung Yoon, Jiwoo Han, Kyung Lib Jang
Summary: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human pathogens causing liver diseases globally. Coinfection of HBV and HCV is often observed in endemic areas, and studies suggest that HBV X protein (HBx) stimulates HCV replication via DNA methylation, providing insight into the dominance of HCV during coinfection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Chemistry, Medicinal
Nicholas A. Meanwell, Mark R. Krystal, Beata Nowicka-Sans, David R. Langley, David A. Conlon, Martin D. Eastgate, Dennis M. Grasela, Peter Timmins, Tao Wang, John F. Kadow
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Pharmacology & Pharmacy
Xiaoliang Zhuo, Ying-Zi Wang, Kap-Sun Yeung, Juliang Zhu, Xiaohua Stella Huang, Kyle E. Parcella, Kyle J. Eastman, John F. Kadow, Nicholas A. Meanwell, Yue-Zhong Shu, Benjamin M. Johnson
Article
Chemistry, Medicinal
Yan Chen, Sing-Yuen Sit, Jie Chen, Jacob J. Swidorski, Zheng Liu, Ny Sin, Brian L. Venables, Dawn D. Parker, Beata Nowicka-Sans, Zeyu Lin, Zhufang Li, Brian J. Terry, Tricia Protack, Sandhya Rahematpura, Umesh Hanumegowda, Susan Jenkins, Mark Krystal, Ira D. Dicker, Nicholas A. Meanwell, Alicia Regueiro-Ren
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Brian L. Venables, Ny Sin, Alan Xiangdong Wang, Li-Qiang Sun, Yong Tu, Dennis Hernandez, Amy Sheaffer, Min Lee, Cindy Dunaj, Guangzhi Zhai, Diana Barry, Jacques Friborg, Fei Yu, Jay Knipe, Jason Sandquist, Paul Falk, Dawn Parker, Andrew C. Good, Ramkumar Rajamani, Fiona McPhee, Nicholas A. Meanwell, Paul M. Scola
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Michael Bowsher, Sheldon Hiebert, Rongti Li, Alan X. Wang, Jacques Friborg, Fei Yu, Dennis Hernandez, Ying-Kai Wang, Herbert Klei, Ramkumar Rajamani, Kathy Mosure, Jay O. Knipe, Nicholas A. Meanwell, Fiona McPhee, Paul M. Scola
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Yong-Jin Wu, Jason Guernon, Andrea McClure, Brian Venables, Ramkumar Rajamani, Kevin J. Robbins, Ronald J. Knox, Michele Matchett, Rick L. Pieschl, James Herrington, Linda J. Bristow, Nicholas A. Meanwell, Richard Olson, Lorin A. Thompson, Carolyn Dzierba
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
B. Narasimhulu Naidu, Michael A. Walker, Margaret E. Sorenson, Yasutsugu Ueda, John D. Matiskella, Timothy P. Connolly, Ira B. Dicker, Zeyu Lin, Sagarika Bollini, Brian J. Terry, Helen Higley, Ming Zheng, Dawn D. Parker, Dedong Wu, Stephen Adams, Mark R. Krystal, Nicholas A. Meanwell
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Editorial Material
Chemistry, Medicinal
Carrie Haskell-Luevano, Gunda I. Georg, Shaomeng Wang, Nicholas Meanwell
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Murugaiah A. M. Subbaiah, Nicholas A. Meanwell, John F. Kadow, Lakshumanan Subramani, Mathiazhagan Annadurai, Thangeswaran Ramar, Salil D. Desai, Sarmistha Sinha, Murali Subramanian, Sandhya Mandlekar, Srikanth Sridhar, Shweta Padmanabhan, Priyadeep Bhutani, Rambabu Arla, Susan M. Jenkins, Mark R. Krystal, Chunfu Wang, Ramakanth Sarabu
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Alicia Regueiro-Ren, Jacob J. Swidorski, Zheng Liu, Yan Chen, Ny Sin, Sing-Yuen Sit, Jie Chen, Brian L. Venables, Juliang Zhu, Beata Nowicka-Sans, Tricia Protack, Zeyu Lin, Brian Terry, Himadri Samanta, Sharon Zhang, Zhufang Li, John Easter, Brett R. Beno, Vinod Arora, Xiaohua S. Huang, Sandhya Rahematpura, Dawn D. Parker, Roy Haskell, Kenneth S. Santone, Mark I. Cocket, Mark Krystal, Nicholas A. Meanwell, Susan Jenkins, Umesh Hanumegowda, Ira B. Dicker
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Yong-Jin Wu, Brian Venables, Jason Guernon, Jie Chen, Sing-Yuen Sit, Ramkumar Rajamani, Ronald J. Knox, Michele Matchett, Rick L. Pieschl, James Herrington, Linda J. Bristow, Nicholas A. Meanwell, Lorin A. Thompson, Carolyn Dzierba
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Chemistry, Medicinal
Kevin M. Peese, Christopher W. Allard, Timothy Connolly, Barry L. Johnson, Chen Li, Manoj Patel, Margaret E. Sorensen, Michael A. Walker, Nicholas A. Meanwell, Brian McAuliffe, Beatrice Minassian, Mark Krystal, Dawn D. Parker, Hal A. Lewis, Kevin Kish, Ping Zhang, Robert T. Nolte, Jean Simmermacher, Susan Jenkins, Christopher Cianci, B. Narasimhulu Naidu
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Guanglin Luo, Ling Chen, Amy Easton, Amy Newton, Clotilde Bourin, Eric Shields, Kathy Mosure, Matthew G. Soars, Ronald J. Knox, Michele Matchett, Rick L. Pieschl, Debra J. Post-Munson, Shuya Wang, James Herrington, John Graef, Kimberly Newberry, Digavalli V. Sivarao, Arun Senapati, Linda J. Bristow, Nicholas A. Meanwell, Lorin A. Thompson, Carolyn Dzierba
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Editorial Material
Chemistry, Medicinal
Carrie Haskell-Luevano, Nicholas A. Meanwell
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Kap-Sun Yeung, Brett R. Beno, Kathy Mosure, Juliang Zhu, Katherine A. Grant-Young, Kyle Parcella, Prakash Anjanappa, Rajesh Onkardas Bora, Kumaravel Selvakumar, Yin-Kai Wang, Hua Fang, Rudolph Krause, Karen Rigat, Mengping Liu, Julie Lemm, Steven Sheriff, Mark Witmer, Jeffrey Tredup, Adam Jardel, Kevin Kish, Dawn Parker, Roy Haskell, Kenneth Santone, Nicholas A. Meanwell, Matthew G. Soars, Susan B. Roberts, John F. Kadow
ACS MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
