Article
Gastroenterology & Hepatology
Raphael Wolfisberg, Caroline E. Thorselius, Eduardo Salinas, Elizabeth Elrod, Sheetal Trivedi, Louise Nielsen, Ulrik Fahnoe, Amit Kapoor, Arash Grakoui, Charles M. Rice, Jens Bukh, Kenn Holmbeck, Troels K. H. Scheel
Summary: An infectious reverse genetic cell culture system for RHV-rn1 has been established, demonstrating hallmark characteristics similar to HCV and infectivity in mice and rats, the study also indicates that adaptive immune pressure is a primary driver of reversion in RHV.
Article
Biochemistry & Molecular Biology
Anita Toscani, Rossana Denaro, Sergio Fernando Castillo Pacheco, Matteo Biolatti, Silvia Anselmi, Valentina Dell'Oste, Daniele Castagnolo
Summary: A series of amidinourea compounds have been synthesized as potential non-nucleoside anti-HSV agents, showing micromolar activity against HSV-1 with low cytotoxicity. These compounds act in an early stage of the HSV replication cycle, just after viral attachment and entry.
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)
Review
Oncology
Yutaka Tsutsumi, Shinichi Ito, Souichi Shiratori, Takanori Teshima
Summary: The hepatitis C virus (HCV) can lead to liver cancer and is associated with lymphoma. Advances in drug treatment have improved outcomes, with the potential for HCV eradication using direct acting antivirals (DAA). HCV reactivation during lymphoma treatment and the role of HCV-RNA as a biomarker are also explored in this review.
Article
Cell Biology
Woan-Ing Twu, Ji-Young Lee, Heeyoung Kim, Vibhu Prasad, Berati Cerikan, Uta Haselmann, Keisuke Tabata, Ralf Bartenschlager
Summary: Although the viral DMVs are structurally similar to autophagosomes, traditional macroautophagy is not essential for the replication of HCV and SARS-CoV-2. These viruses instead utilize factors involved in autophagosome formation, particularly class III phosphatidylinositol 3-kinase (PI3K).
Review
Biochemistry & Molecular Biology
Ja Yeon Kim Chu, Jing-hsiung James Ou
Summary: HCV utilizes cellular autophagy pathway to promote its replication, regulating autophagy through various mechanisms to control intracellular protein and membrane trafficking, thereby enhancing replication and suppressing host innate immune responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Michael P. Schwoerer, Alexander Ploss
Summary: HCV is unable to infect mice due to incompatibility with host factors, the presence of dominant restriction factors, and effective immune responses. Understanding these limitations will help in developing an immunocompetent mouse model that can fully support HCV infection and exhibit disease similar to that of infected humans.
CURRENT OPINION IN VIROLOGY
(2022)
Review
Virology
Susannah Stephenson-Tsoris, T. Jake Liang
Summary: This review provides a comprehensive overview of the interaction between hepatitis delta virus (HDV) and host factors, focusing on the mechanisms involved in viral replication. The article also discusses the implications of these interactions for therapeutic development.
Article
Virology
Susannah Stephenson-Tsoris, John L. Casey
Summary: This study identified the start site for HDV genome RNA synthesis as position 1646 and revealed some differences in the synthesis process. The findings are important for targeting virus replication.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marylin Rheault, Sophie E. Cousineau, Danielle R. Fox, Quinn H. Abram, Selena M. Sagan
Summary: In this study, the different roles of miR-122 in the HCV life cycle were isolated and evaluated using mutations, mutant miRNAs, and HCV luciferase reporter RNAs. The results indicate that the riboswitch has minimal contribution, while genome stability and translational promotion have similar contributions in the establishment phase of infection. However, in the maintenance phase, translational promotion becomes the dominant role. Additionally, an alternative conformation of the 5' untranslated region, termed SLIIalt, was found to be important for efficient virion assembly.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Pu Chen, Justyna Aleksandra Wojdyla, Ombretta Colasanti, Zhijian Li, Bo Qin, Meitian Wang, Volker Lohmann, Sheng Cui
Summary: This study identified a previously unfound activity of HAV 2C, which is a ribonuclease activity. The crystal structure of an HAV 2C fragment was determined, and the importance of the PBD-Pocket interaction for 2C functions was demonstrated. Furthermore, it was found that other picornavirus 2Cs also possess ribonuclease activity.
NUCLEIC ACIDS RESEARCH
(2022)
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
Infectious Diseases
Harry E. Prince, Elizabeth M. Marlowe, Dale S. Schwab
Summary: The study found that some samples with low HCV IgG indices were still HCV RNA positive, with low viral loads. Therefore, it supports the recommendation to test all HCV IgG-reactive sera for HCV RNA.
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
(2021)
Article
Pharmacology & Pharmacy
Andrew M. Skidmore, Steven B. Bradfute
Summary: This systematic review provides a comprehensive summary of the historical knowledge and recent research on alphaviruses, highlighting their impact on human health, agriculture, and their potential as biological warfare and terrorism agents.
ANTIVIRAL RESEARCH
(2023)
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)
Review
Biochemistry & Molecular Biology
Silvia Anselmi, Nandini Aggarwal, Thomas S. Moody, Daniele Castagnolo
Summary: Sulfoxides, important organic compounds widely used in pharmaceutical and organic chemistry, can be synthesized enantioenriched through various biocatalytic approaches. Recent advances include the use of reductive enzymes and unconventional solvents, such as ionic liquids and deep eutectic solvents, for greener and more sustainable synthetic pathways.
Article
Chemistry, Medicinal
Anita Toscani, Charlotte Hind, Melanie Clifford, Seong-Heun Kim, Antonia Gucic, Charlotte Woolley, Naima Saeed, Khondaker Miraz Rahman, J. Mark Sutton, Daniele Castagnolo
Summary: The study reports the synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms. These PhotoCORMs release CO under blue light irradiation and show effective antibacterial activity against multidrug-resistant bacteria, with potential applications in combating antimicrobial resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Dorothy Semenya, Meir Touitou, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Luca Pisano, Vinayak Singh, Kelly Chibale, Georg Bano, Anita Toscani, Fabrizio Manetti, Beatrice Gianibbi, Daniele Castagnolo
Summary: A series of indolyl-3-methyleneamines were designed and synthesized for investigation as new chemical entities against Mycobacterium tuberculosis (Mtb). Compound 7j displayed potent activity and may inhibit Mtb through a unique mechanism.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Fei Zhao, Kate Lauder, Siyu Liu, James D. Finnigan, Simon B. R. Charnock, Simon J. Charnock, Daniele Castagnolo
Summary: This study describes the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of chiral beta-hydroxysulfides using ketoreductase enzymes. Four ketoreductases were discovered and isolated, enabling the synthesis of beta-hydroxysulfides with different configurations. By utilizing novel chemoenzymatic and biocatalytic reactions or dynamic kinetic resolution, high enantioselective synthesis was achieved using commercially available starting materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Maria Grazia Martina, Filomena Sannio, Emmanuele Crespan, Marialaura Pavone, Alice Simoncini, Francesca Barbieri, Cecilia Perini, Emanuela Pesce, Giovanni Maga, Nicoletta Pedemonte, Jean-Denis Docquier, Marco Radi
Summary: CF is a genetic disease caused by mutations in the CFTR gene, leading to negative effects on multiple organs, particularly accumulation of thick mucus in the lungs and chronic respiratory infections. Lung function decline is associated with bacterial infections requiring antibiotic treatments. Developing multifunctional antibiotics tailored to CF may simplify therapeutic approach.
Article
Chemistry, Medicinal
Guilherme F. S. Fernandes, Andrew M. Thompson, Daniele Castagnolo, William A. Denny, Jean L. Dos Santos
Summary: Tuberculosis (TB) has taken more lives than any other infectious disease in the past 2000 years. Despite the comparable death toll with COVID-19 in 2020, the World Health Organization emphasizes the need for new TB drugs to end this pandemic. However, only a small fraction of the promising anti-TB compounds reported annually successfully reach clinical development.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Virology
Andrea Magri, James M. Harris, Valentina D'Arienzo, Rosalba Minisini, Frank Juhling, Peter A. C. Wing, Rachele Rapetti, Monica Leutner, Barbara Testoni, Thomas F. Baumert, Fabien Zoulim, Peter Balfe, Mario Pirisi, Jane A. McKeating
Summary: Chronic hepatitis B virus (HBV) infection is a global health problem that is characterized by interactions between the virus and the host immune system, leading to a spectrum of liver disease. The study investigates the contribution of HBV genomes, including episomal covalently closed circular DNA (cccDNA) and chromosomal integrants, to viral transcripts in chronic hepatitis B (CHB). The results demonstrate that cccDNA-derived transcripts are associated with liver inflammation markers, while integrant-derived transcripts are significantly associated with increasing age but not with inflammatory status.
Article
Chemistry, Medicinal
Dorothy Semenya, Meir Touitou, Domiziana Masci, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Guilherme Felipe Dos Santos Fernandes, Beatrice Gianibbi, Fabrizio Manetti, Daniele Castagnolo
Summary: The exploration around the 2,5-dimethylpyrrole scaffold of antitubercular hit compound 1 has led to the discovery of new derivatives that are active against Mycobacterium tuberculosis and multidrug-resistant clinical isolates. Some of these derivatives showed promising cytotoxicity profiles and were effective in inhibiting the growth of intracellular mycobacteria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Maria Grazia Martina, Carmine Giorgio, Marika Allodi, Simone Palese, Elisabetta Barocelli, Vigilio Ballabeni, Martyna Szpakowska, Andy Chevigne, Jan Piet van Hamburg, Nadine Davelaar, Erik Lubberts, Simona Bertoni, Marco Radi
Summary: The study identifies a new pharmacological approach for the treatment of inflammatory bowel diseases (IBDs) based on small-molecule CCR6 antagonists. The most promising compound was identified using in silico studies and in vitro assays and its efficacy was validated in mouse models. This research provides a theoretical foundation for the development of orally bioavailable drugs for the treatment of IBD and other diseases regulated by the CCL20/CCR6 axis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Organic
Maria Grazia Martina, Lisa Giannessi, Marco Radi
Summary: It is widely recognized that the building blocks of life, purines and pyrimidines, were created through multicomponent reactions on early abiotic Earth. These structures evolved into biologically relevant molecules and served as templates for drug development. The synthetic community has dedicated efforts to replicate the abiotic synthesis of purines and pyrimidines, resulting in the development of various multicomponent synthesis methods. The importance of multicomponent synthesis of new heterocycles is highlighted by the shift towards green chemistry and pharmaceutical sustainability. This review provides an overview of the most important multicomponent approaches for synthesizing purine and pyrimidine derivatives for potential pharmacological applications.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Maria Grazia Martina, Federica Giammarino, Ilaria Vicenti, Elisabetta Groaz, Jef Rozenski, Matteo Incerti, Filomena Sannio, Jean Denis Docquier, Maurizio Zazzi, Marco Radi
Summary: The increasing number of viral outbreaks in recent years calls for the development of novel broad-spectrum antivirals. Non-natural nucleosides have shown to be successful in treating infectious diseases and new base-modified nucleosides were developed for potential antimicrobial activity against different viruses and bacteria.
Article
Pharmacology & Pharmacy
Marika Allodi, Carmine Giorgio, Matteo Incerti, Domenico Corradi, Lisa Flammini, Vigilio Ballabeni, Elisabetta Barocelli, Marco Radi, Simona Bertoni
Summary: This study aims to further investigate the effects of MR120 on chronic colitis and evaluate its anti-inflammatory effect on a mouse model of chronic colitis induced by DSS. The results showed that MR120 significantly improved the health conditions of the mice and attenuated multiple systemic and local inflammatory responses caused by inflammation. Although more potent analogues are needed for clinical translation, this study provides valuable evidence of the in vivo efficacy of CCL20/CCR6 modulators in a chronic model of IBD.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Silvia Anselmi, Alexandra T. P. Carvalho, Angela Serrano-Sanchez, Jose L. Ortega-Roldan, Jill Caswell, Iman Omar, Gustavo Perez-Ortiz, Sarah M. Barry, Thomas S. Moody, Daniele Castagnolo
Summary: This study identifies selective and robust MsrA biocatalysts capable of efficiently catalyzing enantioselective reduction of various aromatic and aliphatic chiral sulfoxides at concentrations of 8-64 mM with high yields and excellent enantiomeric excess (up to 99%). Through rational mutagenesis design using in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies, a mutant enzyme MsrA33 was developed, which can catalyze the kinetic resolution of bulky sulfoxide substrates with non-methyl substituents on the sulfur atom with enantiomeric excess up to 99%, overcoming a significant limitation of current MsrA biocatalysts.
Article
Chemistry, Physical
Haoyue Xiang, Salvatore Ferla, Carmine Varricchio, Andrea Brancale, Nicola L. Brown, Gary W. Black, Nicholas J. Turner, Daniele Castagnolo
Summary: Two enzymatic strategies were developed to oxidize 1,2,3,4-tetrahydroquinolines (THQs) and N-cyclopropyl-N-alkylanilines into quinolines and 2-quinolones, respectively. Whole cells and monoamine oxidase (MAO-N) enzymes were used for the biotransformation of THQs, while horseradish peroxidase (HRP)-catalyzed annulation/aromatization reaction followed by Fe-mediated oxidation was employed for the conversion of N-cyclopropyl-N-alkylanilines into 2-quinolone compounds.
Review
Biochemistry & Molecular Biology
Guilherme Felipe Santos Fernandes, Caue Benito Scarim, Seong-Heun Kim, Jingyue Wu, Daniele Castagnolo
Summary: Oxazolidinone is a five-member heterocyclic ring with diverse applications in medicinal chemistry. Among the isomers, 2-oxazolidinone has been extensively explored and numerous analogues have been developed. Despite promising pharmacological applications in various therapeutic areas, most oxazolidinone derivatives have not progressed beyond the initial stages of drug development. This review highlights the efforts of medicinal chemists in exploring this scaffold and emphasizes its potential for medicinal chemistry.
RSC MEDICINAL CHEMISTRY
(2023)
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)
