Review
Immunology
Kangchen Li, Qianting Ji, Shibo Jiang, Naru Zhang
Summary: This review discusses the pathogenesis of ZIKV infection and summarizes the progress in the development of therapeutics against ZIKV infection, providing guidance for the development of effective therapeutics.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Virology
Ittipat Meewan, Sergey A. Shiryaev, Julius Kattoula, Chun-Teng Huang, Vivian Lin, Chiao-Han Chuang, Alexey V. Terskikh, Ruben Abagyan
Summary: In this study, a virtual docking screening was carried out to target a hydrophobic pocket of ZIKV NS2B-NS3 protease. Six compounds were identified to inhibit the proteolytic activity of the enzyme at low micromolar concentrations. These compounds serve as unique drug candidates against ZIKV and provide new opportunities for the treatment of flavivirus infections.
Article
Biochemistry & Molecular Biology
S. Pant, G. Bhattacharya, N. R. Jena
Summary: This study investigates peptide inhibitors targeting the NS2B-NS3 protease of ZIKV and finds that the YKKR peptide inhibitor forms the most stable complex with the protease and strongly inhibits ZIKV proliferation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Zafirah Liyana Abdullah, Hui-Yee Chee, Rohana Yusof, Fazlin Mohd Fauzi
Summary: This study aimed to repurpose old drugs as novel DENV NS3 inhibitors. Predictive models were built using bioactivity data to screen for potential NS3 inhibitors. In vitro validation showed moderate inhibitory effects of selected drugs and proposed compounds against DENV.
Review
Chemistry, Multidisciplinary
Ashley N. Matthew, Florian Leidner, Gordon J. Lockbaum, Mina Henes, Jacqueto Zephyr, Shurong Hou, Desaboini Nageswara Rao, Jennifer Timm, Linah N. Rusere, Debra A. Ragland, Janet L. Paulsen, Kristina Prachanronarong, Djade Soumana, Ellen A. Nalivaika, Nese Kurt Yilmaz, Akbar Ali, Celia A. Schiffer
Summary: The article discusses the prevalence of drug resistance across various diseases and emphasizes the importance of proactive strategies in drug design and development to minimize the impact of resistance. It also highlights the lessons learned from antiviral drug resistance mechanisms and rational strategies to avoid resistance in drug design.
Article
Chemistry, Medicinal
Naia Pora Santos, Lucianna Helene Santos, Mariana Torquato Quezado de Magalhaes, Jian Lei, Rolf Hilgenfeld, Rafaela Salgado Ferreira, Lucas Bleicher
Summary: A new allosteric pocket in ZIKV NS2B-NS3pro, which is connected to its active site, has been characterized in this study. Experimental evidence shows that the residue Ala125 is involved in covalent bond formation and enzyme inhibition.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Medicine, General & Internal
Suyash Pant, Nihar R. Jena
Summary: This study employs MD simulation and MM/GBSA techniques to design potent peptide inhibitors for the Zika virus protease and understand their interactions. The results show that these inhibitors can stabilize the protease activity and the C-terminal extension can further enhance the stability.
FRONTIERS IN MEDICINE
(2022)
Review
Virology
Damiana Antonia de Fatima Nunes, Felipe Rocha da Silva Santos, Sara Thamires Dias da Fonseca, William Gustavo de Lima, Waleska Stephanie da Cruz Nizer, Jaqueline Maria Siqueira Ferreira, Jose Carlos de Magalhaes
Summary: This study identified compounds with inhibitory activity against the Zika virus NS2B-NS3 protease through a systematic review, including both available drugs on the market and new promising compounds. These compounds showed potent anti-Zika virus activity in vitro, making them potential candidates for antiviral drugs against Zika virus.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Pharmacology & Pharmacy
Tadahisa Teramoto, Kyung H. Choi, Radhakrishnan Padmanabhan
Summary: Flaviviruses, including dengue, West Nile, yellow fever, Japanese encephalitis, and Zika virus, are important human pathogens. These viruses cause a range of diseases, from mild symptoms to severe complications. Dengue infections have dramatically increased in recent decades, causing millions of infections and thousands of deaths each year. Zika virus and West Nile virus also pose significant threats to human health, especially to pregnant women and children.
ANTIVIRAL RESEARCH
(2023)
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)
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)
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)
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
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
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
Biochemistry & Molecular Biology
Martina Bischetti, Nadine Alaimo, Francesca Nardelli, Pasqualina Punzi, Cristi Amariei, Raffaele Ingenito, Giovana Musco, Mariana Gallo, Daniel Oscar Cicero
Summary: Of-Pis1 is a potent antimicrobial peptide that selectively interacts with bacterial membranes, with low toxicity against human erythrocytes. Its interaction with bacterial membranes is tighter and structurally perturbs lipopolysaccharide micelles. Analysis of its amino acid sequence and composition can be used to design more potent and selective antimicrobial peptides.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Review
Cardiac & Cardiovascular Systems
Tuttolomondo Domenico, Antonelli Rita, Setti Giacomo, Ardissino Diego, Pertinhez Thelma, Gallo Mariana, Niccoli Giampaolo, Nicolini Francesco, Georgaki Maria, Formica Francesco, Borrello Bruno, Meleti Marco, Cassi Diana
Summary: Salivary biomarkers, such as cardiac troponin, C-reactive protein, and adiponectin, show potential for the early identification of acute myocardial infarction (AMI). However, further studies are needed to confirm their effectiveness as substitutes for serological markers.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mariana Gallo, Simone Luti, Fabio Baroni, Ivan Baccelli, Eduardo Maffud Cilli, Costanza Cicchi, Manuela Leri, Alberto Spisni, Thelma A. A. Pertinhez, Luigia Pazzagli
Summary: Cerato-ulmin (CU) is a hydrophobin protein that self-assembles at hydrophobic-hydrophilic interfaces, altering the wettability properties of the bound surface. It can elicit a defense reaction in non-host plants and its efficacy is higher in its soluble monomeric form. The protein's hydrophobic clusters on the loops exhibit reversible conformational changes when interacting with hydrophilic or hydrophobic surfaces, suggesting their involvement in the protein's defense elicitation capability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Simone Esposito, Alain Krick, Olivier Pasquier, Fabrice Bonche, Raffaele Ingenito, Paola Magotti, Elisabetta Bianchi, Edith Monteagudo, Mariana Gallo, Daniel Oscar Cicero, Laura Orsatti, Maria Veneziano, Fulvia Caretti, Riccardo Mele, Daniela Roversi, Nadia Gennari, Denis Brasseur, Laurence Gauzy-Lazo, Olivier Duclos, Christine Mauriac, Stephane Illiano, Sergio Mallart
Summary: We have recently identified C18 fatty acid acylated peptides as potent long-lasting single-chain RXFP1 agonists with relaxin-like activities in vivo. Early pharmacokinetics and toxicological studies revealed significant oxidative metabolism of these stearic acid acylated peptides in dog and minipig, with lesser extent in monkey and rat. Mass spectrometry combined with NMR spectroscopy studies showed unexpected oxidation at omega-1, omega-2, and omega-3 positions on the stearic acid chain. In vitro experiments using liver microsomes and engineered bacterial CYPs generated the oxidized metabolites, suggesting the involvement of unknown CYP enzymes in this biotransformation pathway.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Chemistry, Medicinal
Antonella Ilenia Alfano, Sveva Pelliccia, Giacomo Rossino, Orazio Chianese, Vincenzo Summa, Simona Collina, Margherita Brindisi
Summary: The handling of hazardous, toxic, and pollutant chemicals and high-risk intermediates remains a challenge for the efficacy, safety, and scale-up of chemical rearrangements. However, continuous-flow technology has emerged as a powerful tool for driving these reactions, offering easy, controlled, and safer chemistry protocols with minimal side products and increased reaction yields. This Technology Note provides an overview of recent chemical rearrangements using continuous-flow approaches, focusing on Curtius, Hofmann, and Schmidt reactions, and showcases their advantages, safety aspects, and applications in generating privileged scaffolds and active pharmaceutical ingredients.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Oncology
Rita Canella, Federica Brugnoli, Mariana Gallo, Jeffrey W. Keillor, Anna Terrazzan, Elena Ferrari, Silvia Grassilli, Eric W. J. Gates, Stefano Volinia, Valeria Bertagnolo, Nicoletta Bianchi, Carlo M. Bergamini
Summary: This study investigates the role of transglutaminase 2 (TG2) within the cell and its interaction with the voltage-dependent Kv10.1 K+ channel, which is an important target in breast cancer therapies. The use of TG2 inhibitors selectively affects the membrane current of triple-negative cells. The findings highlight the interference of TG2 inhibitors with the Kv10.1 channel as a potential therapeutic tool depending on the specific features of cancer cells.
Article
Biochemistry & Molecular Biology
Maria Maisto, Vincenzo Piccolo, Ettore Novellino, Elisabetta Schiano, Fortuna Iannuzzo, Roberto Ciampaglia, Vincenzo Summa, Gian Carlo Tenore
Summary: The study optimized the extraction process of Ursolic acid (UA) from Annurca apple (AA) using sunflower oil as a solvent, and identified twenty-three phenolic and terpenoid molecules in the extract. The optimized extract, named Optimized Annurca Apple Oleolyte (OAAO), showed significant antioxidant activity and could be considered a safe and functional ingredient for cosmetic formulations.
Article
Biochemistry & Molecular Biology
Giulia Unali, Giovanni Crivicich, Isabel Pagani, Monah Abou-Alezz, Filippo Folchini, Erika Valeri, Vittoria Matafora, Julie A. Reisz, Anna Maria Sole Giordano, Ivan Cuccovillo, Giacomo M. Butta, Lorena Donnici, Angelo D'Alessandro, Raffaele De Francesco, Lara Manganaro, Davide Cittaro, Ivan Merelli, Carolina Petrillo, Angela Bachi, Elisa Vicenzi, Anna Kajaste-Rudnitski
Summary: The interferon-induced transmembrane proteins (IFITM) inhibit endocytic viral entry by binding to phosphatidylinositol 3,4,5-trisphosphate (PIP3), which plays a key role in endosomal antiviral immunity. The level of PIP3 is closely correlated with the potency of endosomal IFITM restriction, and exogenous PIP3 enhances the inhibition of endocytic viruses. These findings elucidate cell-compartment-specific antiviral mechanisms and have potential relevance for the development of broadly acting antiviral strategies.
Article
Medicine, Research & Experimental
Valeria Fumagalli, Pietro Di Lucia, Micol Rava, Davide Marotta, Elisa Bono, Stefano Grassi, Lorena Donnici, Rolando Cannalire, Irina Stefanelli, Anastasia Ferraro, Francesca Esposito, Elena Pariani, Donato Inverso, Camilla Montesano, Serena Delbue, Stanley Perlman, Enzo Tramontano, Raffaele De Francesco, Vincenzo Summa, Luca G. Guidotti, Matteo Iannacone
Summary: Nirmatrelvir, an antiviral drug, reduces the risk of severe COVID-19 but inhibits the development of SARS-CoV-2-specific immune responses. It decreases the production of antibodies and T cells, and affects the quantity of memory T and B cells. These findings have important implications for clinical management and may explain post-treatment relapse in some individuals.
EMBO MOLECULAR MEDICINE
(2023)
Article
Chemistry, Medicinal
Antonella Ilenia Alfano, Sveva Pelliccia, Giacomo Rossino, Orazio Chianese, Vincenzo Summa, Simona Collina, Margherita Brindisi
Summary: In recent years, photochemistry has become increasingly important in academia and the pharmaceutical industry. Continuous-flow chemistry has helped overcome the issues of long photolysis times and light penetration reduction, making photochemical rearrangements more controlled and efficient. This article highlights the benefits of flow chemistry in photochemical rearrangements and showcases recent advances in the synthesis of pharmaceutically relevant substructures using photo-rearrangements in continuous flow.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Food Science & Technology
Elisabetta Schiano, Ilaria Neri, Maria Maisto, Ettore Novellino, Fortuna Iannuzzo, Vincenzo Piccolo, Vincenzo Summa, Lucia Grumetto, Gian Carlo Tenore
Summary: This study developed and validated a method for measuring abscisic acid (ABA) in biological samples using liquid-liquid extraction and liquid mass spectrometry. The researchers found that ABA plays a role in regulating glucose homeostasis in humans, as evidenced by its increase after consuming a standardized test meal. This finding is important for the treatment and monitoring of individuals with dysglycemia.
Article
Biochemistry & Molecular Biology
Mariana Gallo, Elena Ferrari, Anna Terrazzan, Federica Brugnoli, Alberto Spisni, Cristian Taccioli, Gianluca Aguiari, Alessandro Trentini, Stefano Volinia, Jeffrey W. Keillor, Carlo M. Bergamini, Nicoletta Bianchi, Thelma A. Pertinhez
Summary: This study used H-1-NMR metabolomics to investigate the effects of a novel TG2 inhibitor, AA9, on two breast cancer cell lines. The results showed that AA9 promotes apoptosis in both cell lines, with a greater effect on MDA-MB-231. The metabolomics study revealed significant metabolic differences between the two cell lines and provided evidence of AA9's impact on specific metabolic pathways.
Review
Biochemistry & Molecular Biology
Maria Maisto, Adua Marzocchi, Niloufar Keivani, Vincenzo Piccolo, Vincenzo Summa, Gian Carlo Tenore
Summary: In the last decade, obesity has become a dangerous global pandemic, increasing the risk of chronic diseases. The search for natural alternatives to conventional treatments is a current research focus. This review examines the anti-obesity potential of natural chalcones based on in vitro and animal studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Nunzia Maisto, Dalila Mango, Andrea Bettucci, Gaetano Barbato, Maria Grazia Ammendolia, Federica Rinaldi, Carlotta Marianecci, Robert Nistico, Maria Carafa
Summary: Intranasal drug delivery could be a promising strategy for improving drug localization in the brain. In this study, non-ionic surfactant vesicles and nanobubbles were designed and characterized for nose to brain delivery. The results showed that both systems are suitable for this delivery route and can stably release therapeutic drugs.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Roberto Speziale, Camilla Montesano, Giulia Di Pietro, Daniel Oscar Cicero, Vincenzo Summa, Edith Monteagudo, Laura Orsatti
Summary: Huntington's disease (HD) is a genetic condition caused by the expansion of a specific sequence in the huntingtin gene. There is a lack of effective treatments for HD, highlighting the need for reliable mouse models for preclinical studies. This study utilized a urinary liquid chromatography-high-resolution mass spectrometry analysis to identify metabolic changes in different HD mouse models, aiming to improve our understanding of the disease and identify potential biomarkers.
