Article
Immunology
Alba Rodriguez-Garcia, Maria Linares, Maria Luz Morales, Sophie Allain-Maillet, Nicolas Mennesson, Ricardo Sanchez, Rafael Alonso, Alejandra Leivas, Alfredo Perez-Rivilla, Edith Bigot-Corbel, Sylvie Hermouet, Joaquin Martinez-Lopez
Summary: This study reports on the association between HCV infection and the progression of MGUS and MM. The results suggest a causal relationship and show that antiviral treatment can lead to better disease progression. When HCV is eliminated, clonal plasma cells can be controlled, providing new possibilities for the treatment of MGUS and myeloma.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Kai Zhang, Xinyuan Lai, Ji Song, Lingyuan He, Luwei Wang, Guomin Ou, Xing Tian, Lei Wang, Juan Deng, Jiajia Zhang, Chuanyun Li, Hui Zhuang, Tong Li, Kuanhui Xiang
Summary: The coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) can lead to severe liver disease, but a robust HBV/HCV coinfection cell culture model has been established to investigate their interaction. This model supports infection and replication of both HBV and HCV, allowing for a better understanding of their molecular details and outcomes.
ANTIVIRAL RESEARCH
(2021)
Article
Microbiology
Yuanyuan Jia, Wei Yue, Qinghua Gao, Rui Tao, Yaxiang Zhang, Xiaoyang Fu, Yang Liu, Li Liu, Yue Feng, Xueshan Xia
Summary: This study investigated the genetic diversity of hepatitis C virus (HCV), particularly in relation to genotype 6, and identified a new HCV-6 subtype, 6xj, in Yunnan, China. A case of treatment failure showed suspected antiviral resistance mutations, NS5A V28M and NS5B A442V. The findings further confirmed the high diversity of the HCV-6 genotype.
MICROBIOLOGY SPECTRUM
(2021)
Article
Biochemistry & Molecular Biology
Franck Amblard, Sebastien Boucle, Leda Bassit, Zhe Chen, Ozkan Sari, Bryan Cox, Kiran Verma, Tugba Ozturk, Olivia Ollinger-Russell, Raymond F. Schinazi
Summary: A study has identified a new compound, GLP-26, that significantly impacts HBV infection by inhibiting viral DNA replication, reducing antigen secretion, and affecting the maintenance of cccDNA. This compound shows promising pre-clinical results and long-term effects on viral loads in a humanized mouse model.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Veterinary Sciences
Manyu Li, Yan Wang, Kejian Li, Haiyun Lan, Cheng Zhou
Summary: In this study, key genes in the chronic infection of Hepatitis E virus (HEV) in rabbits were investigated using bioinformatics and experimental analysis. MX1, OAS2, and IFI44 were found to be significantly upregulated in rabbits with chronic HEV infection, suggesting their potential involvement in the pathogenesis of HEV chronicity.
BMC VETERINARY RESEARCH
(2022)
Article
Agriculture, Multidisciplinary
Ningning Zan, Jiao Li, Hongfu He, Deyu Hu, Baoan Song
Summary: Novel chromone derivatives containing dithioacetals were prepared and evaluated for their antiviral activity against tomato spotted wilt virus (TSWV). Compounds A32 and A33 exhibited excellent anti-TSWV activities, surpassing the control agents ningnanmycin and ribavirin. Compound A33 was found to inhibit TSWV by blocking the interaction between TSWV N and viral RNA, making it a potential antiviral agent targeting TSWV N.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Review
Gastroenterology & Hepatology
Alessandra Mangia, Rosa Cotugno, Giovanna Cocomazzi, Maria Maddalena Squillante, Valeria Piazzolla
Summary: The World Health Organization's goal of eliminating Hepatitis C virus (HCV) by 2030 using direct-acting antiviral treatments has become less attainable post the 2020 pandemic of coronavirus disease 2019. Therefore, a more realistic approach of micro-elimination in population segments where targeted strategies of prevention and treatment are easily attained has been promoted in Europe. Active involvement of stakeholders and community participation are essential components for the success of a micro-elimination project tailored at the geographical level according to HCV epidemiology and individual country's income.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Microbiology
Dara Burdette, Anastasia Hyrina, Zhijuan Song, Rudolf K. Beran, Tara Cheung, Sarah Gilmore, Tetsuya Kobayashi, Li Li, Yang Liu, Anita Niedziela-Majka, Jonathan Medley, Upasana Mehra, Philip Morganelli, Nikolai Novikov, Congrong Niu, Danny Tam, Jennifer Tang, Jianhong Wang, Qin Yue, Simon P. Fletcher, Meghan M. Holdorf, William E. Delaney, Becket Feierbach, Scott Lazerwith
Summary: The standard treatment for chronic hepatitis B involves lifelong use of nucleos(t)ide analogs (NAs) to suppress viral replication. However, these agents fail to cure most patients and infectious virus can still be detected in virally suppressed patients. Therefore, new antiviral treatment options are being developed to enhance the suppression of hepatitis B virus (HBV) replication. GS-SBA-1, a capsid assembly modulator (CAM), demonstrated potent inhibition of extracellular HBV DNA both in vitro and in vivo, and showed comparable activities across different HBV genotypes and drug-resistant mutants. GS-SBA-1 also showed additive effects in combination with tenofovir alafenamide (TAF). Furthermore, GS-SBA-1 prevented the formation of covalently closed circular DNA (cccDNA) and decreased HBV RNA and antigen levels, as well as the production of extracellular HBV RNA-containing viral particles in vitro.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Virology
Modhusudon Shaha, Sumen Majumder, Md Saddam Hossain, Munira Jahan, Raad Rahmat, Ridwana Asma, Mohammad Ariful Islam, Md. Hadisur Rahman, Keshob Chandra Das, Palash Kumar Sarker, Mamun Al Mahtab, Sheikh Mohammad Fazle Akbar, Md Salimullah
Summary: This study reports a novel variant of HBV in a patient co-infected with HCV, and identifies unusual genomic modifications in the HBV genome associated with liver cirrhosis.
Article
Chemistry, Medicinal
Mengying Guan, Yuan Wang, Yunwen Wang, Na Chen, Shu Shi, Rong Sheng
Summary: The magic methyl effect strategy was used to design 5-alkyl-2-pyrazol-oxazolidin-4-one derivatives as HBV capsid assembly modulators. These compounds showed potent HBV inhibitory activities with low cytotoxicities in HepG2.2.15 cells. The most promising compounds 9d and 10b had high selectivity and potential therapeutic effects against HBV infection.
ARCHIV DER PHARMAZIE
(2023)
Review
Microbiology
Anshuman Das, Efrain E. Rivera-Serrano, Xin Yin, Christopher M. Walker, Zongdi Feng, Stanley M. Lemon
Summary: In this Review, the authors discuss quasi-enveloped virions, their entry and release from human host cells, and their impact on host immunity and pathogenesis. They focus on hepatitis A and E viruses, which were previously considered non-enveloped but are now known to be released as quasi-enveloped virions cloaked in host membranes. Despite lacking virally encoded proteins on their surface, these virions efficiently enter cells and replicate. The authors also describe the mechanisms by which specific peptide sequences in the capsids of these virions mediate their release from hepatocytes and the current understanding of their cell entry mechanism.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Medicine, General & Internal
Meghan D. Morris, Claire Mcdonell, Annie F. Luetkemeyer, Robert Thawley, Jeff Mckinney, Jennifer C. Price
Summary: This study examines the feasibility, acceptability, and safety of hepatitis C virus (HCV) treatment at the point of diagnosis in a nonclinical community setting. The results show that the test-and-treat model of care reduces steps between testing and treatment initiation, leading to high levels of treatment initiation, completion, and cure.
Article
Immunology
Qingqin Hao, Qinghui Wang, Huizhong Qian, Jian Jiang, Xiao Liu, Wei Xia
Summary: This study found that miR-451a and miR-340-3p were significantly up-regulated in plasma of OBI, ASC, and CHB patients compared to healthy controls. ROC curve analysis showed that both miR-451a and miR-340-3p could moderately distinguish OBI from HCs. Functional experiments demonstrated that overexpression of miR-451a might suppress HBV replication and gene expression by directly targeting ATF2.
MICROBIAL PATHOGENESIS
(2021)
Review
Gastroenterology & Hepatology
Patricia Holanda Almeida, Celso E. L. Matielo, Lilian A. Curvelo, Rodrigo A. Rocco, Guilherme Felga, Bianca Della Guardia, Yuri L. Boteon
Summary: Significant progress has been made in the treatment of viral hepatitis, including curative therapies for hepatitis C and advancements in vaccination for hepatitis A, B, and E. There is currently no cure for hepatitis B, but targeted antiviral drugs show promise in eradicating the virus. High vaccination coverage and large-scale test-and-treat programs may ultimately eliminate viral hepatitis and reduce the burden on health systems.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Virology
Anni Winckelmann, Ulrik Fahnoe, Priyanka Shukla Bajpai, Magnus Illum Dalegaard, Andreas Lundh, Lene Ryom, Jens Bukh, Nina Weis
Summary: This study investigates the evolution of HBV during tenofovir treatment and identifies potential resistance mutations. The findings suggest that changes at a conserved residue 35 in the HBV RT may be associated with tenofovir resistance. Further studies are needed to assess resistance in vitro and in vivo.
JOURNAL OF CLINICAL VIROLOGY
(2022)
Review
Medicine, Research & Experimental
Karamarie Fecho, Anne E. Thessen, Sergio E. Baranzini, Chris Bizon, Jennifer J. Hadlock, Sui Huang, Ryan T. Roper, Noel Southall, Casey Ta, Paul B. Watkins, Mark D. Williams, Hao Xu, William Byrd, Vlado Dancik, Marc P. Duby, Michel Dumontier, Gustavo Glusman, Nomi L. Harris, Eugene W. Hinderer, Greg Hyde, Adam Johs, Andrew Su, Guangrong Qin, Qian Zhu
Summary: Clinical, biomedical, and translational science are facing challenges in terms of data integration and accessibility. The Biomedical Data Translator Consortium has developed a knowledge graph-based Translator system to address these challenges and provide valuable insights. The system has shown feasibility and made significant progress.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Maria Esteban-Lopez, Kenneth Wilson, Courtney Myhr, Elena Kaftanovskaya, Mark Henderson, Noel Southall, Xin Hu, Elena Barnaeva, Mare Ferrer, David Kim
Meeting Abstract
Biochemistry & Molecular Biology
Amy E. Moritz, Nora S. Madaras, Laura R. Inbody, Amber M. Kelley, Disha M. Gandhi, Emmanuel Akano, Kuo H. Lee, R. B. Free, Xin Hu, Noel T. Southall, Mare Ferrer, Lei Shi, Kevin J. Frankowski, David R. Sibley
Article
Multidisciplinary Sciences
J. D. Gross, D. W. Kim, Y. Zhou, D. Jansen, L. M. Slosky, N. B. Clark, C. R. Ray, X. Hu, N. Southall, A. Wang, X. Xu, E. Barnaeva, W. C. Wetsel, M. Ferrer, J. J. Marugan, M. G. Caron, L. S. Barak, K. Toth
Summary: This study discovered a novel GHSR(1a) agonist called N8279, which exhibits strong selectivity for G protein signaling, providing potential for treating disorders of disrupted dopamine homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Jonathan H. Shrimp, John Janiszewski, Catherine Z. Chen, Miao Xu, Kelli M. Wilson, Stephen C. Kales, Philip E. Sanderson, Paul Shinn, Rick Schneider, Zina Itkin, Hui Guo, Min Shen, Carleen Klumpp-Thomas, Samuel G. Michael, Wei Zheng, Anton Simeonov, Matthew D. Hall
Summary: This study developed a suite of biochemical assays for the discovery and development of new inhibitors of TMPRSS2. Through drug repurposing, a total of 6030 compounds were screened biochemically, and the potential antiviral compounds were evaluated in cell-based experiments.
ACS INFECTIOUS DISEASES
(2022)
Article
Cell Biology
Tamara Marin, Andres E. Dulcey, Fabian Campos, Catalina de la Fuente, Mariana Acuna, Juan Castro, Claudio Pinto, Maria Jose Yanez, Cristian Cortez, David W. McGrath, Pablo J. Saez, Kirill Gorshkov, Wei Zheng, Noel Southall, Maria Carmo-Fonseca, Juan Marugan, Alejandra R. Alvarez, Silvana Zanlungo
Summary: Niemann-Pick type A (NPA) disease is a fatal lysosomal neurodegenerative disorder. Recent studies have shown that c-Abl tyrosine kinase activity plays a role in neuronal damage and death in NPA disease. There is potential for the use of c-Abl inhibitors in the clinical treatment of NPA patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Deepak R. Unni, Sierra A. T. Moxon, Michael Bada, Matthew Brush, Richard Bruskiewich, J. Harry Caufield, Paul A. Clemons, Vlado Dancik, Michel Dumontier, Karamarie Fecho, Gustavo Glusman, Jennifer J. Hadlock, Nomi L. Harris, Arpita Joshi, Tim Putman, Guangrong Qin, Stephen A. Ramsey, Kent A. Shefchek, Harold Solbrig, Karthik Soman, Anne E. Thessen, Melissa A. Haendel, Chris Bizon, Christopher J. Mungall
Summary: Graph-based data models are increasingly used in clinical, biomedical, and translational science projects for knowledge representation. However, knowledge discovery across these knowledge graphs has remained challenging due to data heterogeneity and complexity, proliferation of ad hoc data formats, and a lack of a universally accepted standardization model. The Biolink Model is an open-source model that addresses these challenges by formalizing relationships between data structures in translational science, supporting integration and interoperability of biomedical knowledge graphs.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Kevin J. Frankowski, Samarjit Patnaik, Chen Wang, Noel Southall, Dipannita Dutta, Soumitta De, Dandan Li, Christopher Dextras, Yi-Han Lin, Marthe Bryant-Connah, Danielle Davis, Feijun Wang, Leah M. Wachsmuth, Pranav Shah, Jordan Williams, Md Kabir, Edward Zhu, Bolormaa Baljinnyam, Amy Wang, Xin Xu, John Norton, Marc Ferrer, Steve Titus, Anton Simeonov, Wei Zheng, Lesley A. Mathews Griner, Ajit Jadhav, Jeffrey Aube, Mark J. Henderson, Udo Rudloff, Frank J. Schoenen, Sui Huang, Juan J. Marugan
Summary: The perinucleolar compartment (PNC) is a subnuclear body enriched with RNA transcripts and RNA-binding proteins. PNC prevalence is positively correlated with cancer progression and metastatic capacity. A high-throughput assay was developed to identify small molecules that can reduce PNC prevalence in cancer cells. The discovery of the pyrrolopyrimidine series led to the identification of the bioavailable analogue metarrestin, which has potent antimetastatic activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Ying Fu, Juliana da Fonseca Rezende e Mello, Bryan D. D. Fleming, Alex Renn, Catherine Z. Z. Chen, Xin Hu, Miao Xu, Kirill Gorshkov, Quinlin Hanson, Wei Zheng, Emily M. M. Lee, Lalith Perera, Robert Petrovich, Manisha Pradhan, Richard T. T. Eastman, Zina Itkin, Thomas B. B. Stanley, Allen Hsu, Venkata Dandey, Kedar Sharma, William Gillette, Troy Taylor, Nitya Ramakrishnan, Shelley Perkins, Dominic Esposito, Eunkeu Oh, Kimihiro Susumu, Mason Wolak, Marc Ferrer, Matthew D. D. Hall, Mario J. J. Borgnia, Anton Simeonov
Summary: The study presents a rapid and efficient strategy for developing neutralizing humanized nanobody constructs against SARS-CoV-2. The most potent nanobody identified is capable of neutralizing the B.1.1.7 variant and withstands a specific mutation. Structural analysis and molecular dynamics simulations provide insights into the neutralization process. In an ex vivo model, the nanobody treatment effectively reduces viral burden for different SARS-CoV-2 strains.
Editorial Material
Biotechnology & Applied Microbiology
Alexandre Kiazand, Ruth Luther, Jessica Marlind Wuertele, Noel Southall, Douglas Domalik, Magnus Ysander
Summary: The COVID-19 vaccine effort was the fastest global response to a health crisis in history, allowing for the evaluation and improvement of pharmaceutical industry pharmacovigilance practices to enhance safety signal detection, evaluation, and communication.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Phillip R. Sanchez, Sarah A. Head, Shan Qian, Haibo Qiu, Avishek Roy, Zhendong Jin, Wei Zheng, Jun O. Liu
Summary: ZJ-101, a simplified analog of superstolide A, exhibits potent antiproliferative and antiadhesive effects, making it a potential therapeutic agent. Transcriptomics analysis revealed a unique dysregulation of the endomembrane system by ZJ-101, including selective inhibition of O-glycosylation. In a triple-negative breast cancer spheroid model, ZJ-101 showed potential for reversing 3D-induced chemoresistance, indicating its synergistic therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ivan Pavlinov, Mitali Tambe, Joshua Abbott, Ha Nam Nguyen, Miao Xu, Manisha Pradhan, Atena Farkhondeh, Wei Zheng
Summary: The ability to model human neurological tissues in vitro is crucial for drug development in neurological disorders. iPSC-derived brain organoids can effectively mimic protein expression patterns and physiology of specific brain regions. This study differentiated midbrain-specific brain organoids from iPSC-lines derived from healthy individuals using a matrix-free, bioreactor method. The expression of midbrain-specific neuronal markers was monitored from 7 to 90 days, and the organoids were further characterized using electron microscopy and RNA-seq. The findings provide potential benchmarks for evaluating differentiation protocols and identifying disease phenotypes in midbrain organoids derived from patient iPSC-lines with genetic neurological disorders.
Article
Public, Environmental & Occupational Health
Jiyoon Park, Malek Djelassi, Daniel Chima, Robert Hernandez, Vladimir Poroshin, Ana-Maria Iliescu, Douglas Domalik, Noel Southall
Summary: This study aims to validate an automated deep learning approach to literature surveillance for use at AstraZeneca. The results show that the model demonstrates consistent global performance compared to human surveillance teams. The prospective evaluation of model performance allows for a thorough examination of its consistency and failure modes, qualifying it for use in their surveillance processes.
Article
Microbiology
Seung Bum Park, Parker Irvin, Zongyi Hu, Mohsin Khan, Xin Hu, Qiru Zeng, Catherine Chen, Miao Xu, Madeleine Leek, Ruochen Zang, James Brett Case, Wei Zheng, Siyuan Ding, T. Jake Liang
Summary: Two hepatitis C virus fusion inhibitors have been found to broadly block human coronavirus entry into various cell types, showing effective antiviral activity against SARS-CoV-2 and its variants.
