Review
Biochemistry & Molecular Biology
Agni F. M. Gavriilidou, Kleitos Sokratous, Hsin-Yung Yen, Luigi De Colibus
Summary: Studying protein-ligand interactions can greatly assist in the design of new therapeutic molecules. Various techniques used in drug discovery, such as isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, rely on protein crystallography and cryo-electron microscopy. Native mass spectrometry is a versatile method for studying proteins and their interactions, providing valuable insights into protein structure and thermodynamics.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Immunology
Xiaojing Wen, Li Zhang, Shan Zhao, Qiang Liu, Wenyi Guan, Jiajing Wu, Qiwei Zhang, Hongling Wen, Weijin Huang
Summary: The study found that cardamomin has good anti-human adenovirus 5 (HAdV5) activity both in vitro and in vivo, and can protect tissues from virus-induced damage. This research established a method for high-throughput screening of anti-HAdV5 drugs and demonstrated cardamomin as a potential new treatment for patients infected with adenoviruses.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Physical
Matthew Bain, Jose L. Godinez Castellanos, Stephen E. Bradforth
Summary: High-repetition-rate lasers have the potential to revolutionize ultrafast spectroscopy by enabling routine analysis for machine learning models in the design of photochemical syntheses. In this study, we combine innovations in line scan cameras and micro-electro-mechanical grating modulators with high-pressure liquid chromatography pumps to develop a transient absorption spectrometer that can characterize photoreactions in minutes. Additionally, we demonstrate the utility of this technique in exploring the effects of conformational modification on excited-state processes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Oncology
Niamh H. McCabe, Leanne Stevenson, Enya Scanlon, Rosalie Douglas, Susanna Kennedy, Oliver Keminer, Bjoern Windshuegel, Daniela Zisterer, Richard D. Kennedy, Jaine K. Blayney, Richard C. Turkington
Summary: Oesophageal adenocarcinoma (OAC), a common cancer with poor prognosis, is often resistant to chemotherapy. This study identified targeting Src as a potential strategy to enhance the efficacy of chemotherapy in OAC cells, providing new insights for developing therapeutic approaches.
Article
Multidisciplinary Sciences
Paola Ruiz Puentes, Natalia Valderrama, Cristina Gonzalez, Laura Daza, Carolina Munoz-Camargo, Juan C. Cruz, Pablo Arbelaez
Summary: The discovery and development of new pharmaceuticals is a highly active research area due to the significant investments and long payback times required. The use of in silico approaches to reduce costs has shown limited success, with a machine learning-based algorithm like PharmaNet using Recurrent Neural Networks showing promise for more accurate prediction of pharmacological candidates. This approach significantly outperforms previous methods in terms of predictive accuracy, particularly for predicting potential targets like human farnesyl pyrophosphate synthase (FPPS) with implications for antimicrobial and anticancer treatments.
Article
Pharmacology & Pharmacy
Peng Li, Chujie Bai, Lingmin Zhan, Haoran Zhang, Yuanyuan Zhang, Wuxia Zhang, Yingdong Wang, Jinzhong Zhao
Summary: Identifying the biological targets of a compound is crucial for understanding drug mechanisms and developing new drugs. The Connectivity Map concept connects genes, drugs, and diseases based on gene-expression signatures. However, existing methods are inefficient due to the need for reference drugs. In this study, we developed a procedure to extract target-induced gene modules and identified target gene clusters. Additionally, we proposed a gene module pair-based approach to predict novel compound-target interactions, leading to the discovery of new inhibitors for PI3K pathway proteins.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Priyanka Parijat, Saraswathi Ponnam, Seetharamaiah Attili, Kenneth S. Campbell, Mohammed El-Mezgueldi, Mark Pfuhl, Thomas Kampourakis
Summary: The unmet demand for new heart failure therapeutics is well recognized and targeting the contractile myofilaments has shown potential for the development of new drugs. However, limited clinical use and incomplete understanding of myofilament function have hindered progress in this area. In this study, new high throughput screening platforms were designed and validated to explore the effects of small molecule effectors on the interactions between cardiac troponin C and troponin I subunits. The results suggest that sarcomeric protein-directed screening platforms are suitable for developing compounds that modulate cardiac myofilament function.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Marko Jukic, Rodolphe Auger, Victor Folcher, Matic Proj, Helene Barreteau, Stanislav Gobec, Thierry Touze
Summary: The study identified small molecules that inhibit the activity of BacA, an enzyme involved in the recycling of undecaprenyl pyrophosphate. The compounds showed significant inhibition of the enzyme's activity and also demonstrated antibacterial activity against Escherichia coli strains.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Shasha Liu, Pengfei She, Zehao Li, Yimin Li, Linhui Li, Yifan Yang, Linying Zhou, Yong Wu
Summary: High incidences of urinary tract infection caused by aminoglycosides-resistant E. coli pose a severe burden on public health. This study investigates the antimicrobial activity of the antifungal benzoxaborole drug tavaborole, and its synergistic interaction with aminoglycosides against multidrug resistant E. coli. The results suggest that tavaborole can slow the development of resistance to aminoglycosides and reduce invasiveness of E. coli in combination with tobramycin. Further research is needed to understand the mechanism of action. Tavaborole also exhibits low toxicity and enhances the bactericidal activity of aminoglycosides in an experimental mouse model. These findings indicate the potential of tavaborole as a novel adjuvant to combat drug resistant E. coli and highlight the need for the discovery of more benzoxaborole analogues.
Article
Multidisciplinary Sciences
Zhenzhen Wang, Jiangjiexing Wu, Jia-Jia Zheng, Xiaomei Shen, Liang Yan, Hui Wei, Xingfa Gao, Yuliang Zhao
Summary: The study uses density functional theory calculations to investigate the principles behind the SOD-like catalytic activity of nanomaterials, proposing energy level and adsorption energy principles for quantitatively describing the activity. These principles were validated through experiments on metal-organic frameworks and can be easily implemented in computer programs for screening NMs with intrinsic SOD-like activity. A general predicting theory for superoxide-dismutase mimicking nanomaterials is currently lacking.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Md Kabir, Elias C. Padilha, Pranav Shah, Ruili Huang, Srilatha Sakamuru, Eric Gonzalez, Lin Ye, Xin Hu, Mark J. Henderson, Menghang Xia, Xin Xu
Summary: CYP3A7 is an important xenobiotic metabolizing enzyme in the liver of human embryos, fetuses, and newborns. We identified chemical features important for CYP3A7 selectivity and established a dataset for future drug metabolism and interaction studies.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Xabier Rodriguez-Martinez, Enrique Pascual-San-Jose, Mariano Campoy-Quiles
Summary: The discovery of novel high-performing materials in organic solar cells has rapidly increased efficiency, but traditional experimentation methods are unable to evaluate the vast catalog of materials efficiently. High-throughput experimental and computational methods are being utilized to accelerate the discovery of new materials, with machine-learning algorithms playing a key role in retrieving quantitative structure-activity relationships.
ENERGY & ENVIRONMENTAL SCIENCE
(2021)
Article
Virology
Xiaojing Wen, Li Zhang, Qiang Liu, Xinyue Xiao, Weijin Huang, Youchun Wang
Summary: A high-throughput screening method was developed to identify compounds with inhibitory effects on Hantavirus. Cepharanthine, one of the identified compounds, showed promising activity in vitro and in vivo. These findings could potentially contribute to the treatment of Hantavirus infections.
Article
Chemistry, Multidisciplinary
Zihan Yang, Zhihang Zhou, Tongxu Si, Zhengdong Zhou, Li Zhou, Y. Rebecca Chin, Liang Zhang, Xinyuan Guan, Mengsu Yang
Summary: Cancer metastasis is a major cause of cancer-related death, and it is characterized by excessive extracellular matrix deposition and increased stiffness in solid tumors. The confined migration of tumor cells in these conditions plays a crucial role in metastasis, but inhibitors specifically targeting this type of migration are rare. In this study, a microfluidic chip was designed to screen for drugs that can effectively inhibit confined migration of cancer cells. By applying this chip, three novel inhibitors of confined migration, MA-5, SB-705498, and diphenyleneiodonium chloride, were discovered in multiple cancer types. The mechanisms of action of these inhibitors were found to be targeting mitochondria, actin polymerization, and cell viability, respectively. Overall, a high-throughput microfluidic platform for screening drugs targeting confined migration was established, and three effective inhibitors were identified.
Article
Chemistry, Medicinal
Serena Massari, Chiara Bertagnin, Maria Chiara Pismataro, Anna Donnadio, Giulio Nannetti, Tommaso Felicetti, Stefano Di Bona, Maria Giulia Nizi, Leonardo Tensi, Giuseppe Manfroni, Maria Isabel Loza, Stefano Sabatini, Violetta Cecchetti, Jose Brea, Laura Goracci, Arianna Loregian, Oriana Tabarrini
Summary: This study focuses on finding new anti-flu drugs by targeting the viral RNA-dependent RNA polymerase, synthesizing a series of new compounds, and conducting in-depth research on some of these compounds to identify new compounds with activity to inhibit viral replication.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Correction
Multidisciplinary Sciences
Enrico Lavezzo, Elisa Franchin, Constanze Ciavarella, Gina Cuomo-Dannenburg, Luisa Barzon, Claudia Del Vecchio, Lucia Rossi, Riccardo Manganelli, Arianna Loregian, Nicolo Navarin, Davide Abate, Manuela Sciro, Stefano Merigliano, Ettore De Canale, Maria Cristina Vanuzzo, Valeria Besutti, Francesca Saluzzo, Francesco Onelia, Monia Pacenti, Saverio G. Parisi, Giovanni Carretta, Daniele Donato, Luciano Flor, Silvia Cocchio, Giulia Masi, Alessandro Sperduti, Lorenzo Cattarino, Renato Salvador, Michele Nicoletti, Federico Caldart, Gioele Castelli, Eleonora Nieddu, Beatrice Labella, Ludovico Fava, Matteo Drigo, Katy A. M. Gaythorpe, Alessandra R. Brazzale, Stefano Toppo, Marta Trevisan, Vincenzo Baldo, Christl A. Donnelly, Neil M. Ferguson, Ilaria Dorigatti, Andrea Crisanti, Andrea Crisanti
Summary: The correction to this paper has been published.
Article
Pharmacology & Pharmacy
Beatrice Mercorelli, Marta Celegato, Anna Luganini, Giorgio Gribaudo, Galina Lepesheva, Arianna Loregian
Summary: The new extended-spectrum antifungal drug isavuconazole (ICZ) has broad-spectrum activity against human cytomegalovirus (HCMV), inhibiting both clinical isolates and strains resistant to current DNA polymerase inhibitors. Its antiviral activity against HCMV may be attributed to the inhibition of human cytochrome P450 51 (hCYP51). Additionally, ICZ shows synergistic antiviral effects when combined with approved antiHCMV drugs in vitro.
ANTIVIRAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Ruifang Jia, Jian Zhang, Chiara Bertagnin, Srinivasulu Cherukupalli, Wei Ai, Xiao Ding, Zhuo Li, Jiwei Zhang, Han Ju, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: The structural modifications at the 150-cavity of influenza virus neuraminidases can result in more potent oseltamivir derivatives, with compound 5c showing the most promising activity. In vitro and in vivo studies demonstrated low cytotoxicity and no acute toxicity of 5c, indicating its potential as a drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Lorenzo Messa, Marta Celegato, Chiara Bertagnin, Beatrice Mercorelli, Gualtiero Alvisi, Lawrence Banks, Giorgio Palu, Arianna Loregian
Summary: Understanding the mechanisms of action of HPV oncoproteins is crucial for developing anti-cancer drugs against HPV-related malignancies. This study focused on the mechanism of HPV16 oncoprotein E6, specifically how it targets the YAP/TAZ signaling pathway in cancer cells. The findings revealed the importance of hScrib degradation and the dimeric form of HPV16 E6 in this process, shedding light on E6 homodimerization as a key event for YAP/TAZ upregulation.
Article
Chemistry, Medicinal
Maria Chiara Pismataro, Tommaso Felicetti, Chiara Bertagnin, Maria Giulia Nizi, Anna Bonomini, Maria Letizia Barreca, Violetta Cecchetti, Dirk Jochmans, Steven De Jonghe, Johan Neyts, Arianna Loregian, Oriana Tabarrini, Serena Massari
Summary: The study identified 1,2,4-triazolo[1,5-a] pyrimidine (TZP) as a suitable scaffold for developing anti-influenza virus compounds, with compound 22 showing high activity. Furthermore, the research highlighted the potential of TPZ scaffold in the search for anti-coronavirus agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jenny Desantis, Beatrice Mercorelli, Marta Celegato, Federico Croci, Alessandro Bazzacco, Massimo Baroni, Lydia Siragusa, Gabriele Cruciani, Arianna Loregian, Laura Goracci
Summary: Indomethacin (INM) has shown antiviral activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in drug repurposing studies. Recent research indicates that the antiviral activity of INM could be attributed to its inhibition of human prostaglandin E synthase type 2 (PGES-2). This study explores the application of Proteolysis Targeting Chimeras (PROTACs) technology to develop more potent INM-derived PROTACs with anti-CoV activity, which showed a strong improvement in antiviral potency compared to INM. Molecular modelling studies suggest that human PGES-2 is a potential target of INM-based antiviral PROTACs, paving the way for the development of host-directed anti-coronavirus strategies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Lorenzo Messa, Arianna Loregian
Summary: High-risk HPV infections are associated with various epithelial cancers, but there are currently no specific anti-HPV drugs available. This article provides a comprehensive report on potential small molecule compounds for HPV-driven tumors, categorizing them into non-targeted and targeted agents.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Chemistry, Medicinal
Han Ju, N. Arul Murugan, Lingxin Hou, Ping Li, Laura Guizzo, Ying Zhang, Chiara Bertagnin, Xiujie Kong, Dongwei Kang, Ruifang Jia, Xiuli Ma, Ruikun Du, Vasanthanathan Poongavanam, Arianna Loregian, Bing Huang, Xinyong Liu, Peng Zhan
Summary: The study focused on modifying oseltamivir derivatives targeting the 150-cavity of influenza neuraminidase, resulting in the synthesis of potent anti-influenza compound 23d. Compound 23d showed exceptional antiviral activity against a panel of Group-1 NAs, demonstrating promising potential for the treatment of influenza virus infection.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Lingxin Hou, Ying Zhang, Han Ju, Srinivasulu Cherukupalli, Ruifang Jia, Jian Zhang, Bing Huang, Arianna Loregian, Xinyong Liu, Peng Zhan
Summary: Influenza is a global acute respiratory infectious disease caused by the influenza virus, leading to significant social and economic losses. The viral ribonucleoprotein complex (vRNP) plays a crucial role in the life cycle of influenza viruses and serves as an attractive target for discovering new anti-influenza drugs. Several drug candidates, including baloxavir, have entered clinical trials, with baloxavir already being marketed in Japan and the United States.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Oncology
Marta Celegato, Lorenzo Messa, Chiara Bertagnin, Beatrice Mercorelli, Arianna Loregian
Summary: The compound Cpd12 blocks the interaction between HPV E6 oncoprotein and cellular tumor suppressor p53, exhibiting broad activity against different HPV genotypes and HPV-positive head-and-neck cancer cells. It can also inhibit cancer cell migration and enhance the activity of chemotherapeutic drugs. These findings improve our understanding of the therapeutic potential of Cpd12 and provide a basis for developing new therapies against HPV-induced tumors.
Article
Biochemistry & Molecular Biology
Ruifang Jia, Jiwei Zhang, Jian Zhang, Chiara Bertagnin, Anna Bonomini, Laura Guizzo, Zhen Gao, Xiangkai Ji, Zhuo Li, Chuanfeng Liu, Han Ju, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: Novel boron-containing derivatives were designed and synthesized to address drug resistance to influenza virus. Compound 2c exhibited strong antiviral activity against multiple influenza viruses, low cytotoxicity, and no acute toxicity.
Article
Microbiology
Marta Celegato, Mattia Sturlese, Vivian Vasconcelos Costa, Marta Trevisan, Angelica SamerLallo Dias, Ingredy Beatriz Souza Passos, Celso Martins Queiroz-Junior, Lorenzo Messa, Annagiulia Favaro, Stefano Moro, Mauro Martins Teixeira, Arianna Loregian, Beatrice Mercorelli
Summary: This study identifies two small molecules with pan-flavivirus antiviral potential through virtual screening of over 1 million compounds. The molecules inhibit the replication of dengue virus, Zika virus, and West Nile virus, and show efficacy in a mouse model of dengue.
Article
Chemistry, Medicinal
Ruifang Jia, Jiwei Zhang, Fangyuan Shi, Anna Bonomini, Camilla Lucca, Chiara Bertagnin, Jian Zhang, Chuanfeng Liu, Huinan Jia, Yuanmin Jiang, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: Two series of oseltamivir derivatives were designed, synthesized, and evaluated for their ability to inhibit neuraminidase. Compound 43b showed weaker or slightly improved inhibitory activity against wild-type neuraminidases compared to oseltamivir carboxylate. However, it displayed significantly more potent activity against mutant neuraminidases and exhibited equivalent or more potent antiviral activities in cellular assays. Additionally, 43b possessed improved physicochemical properties and ADMET properties compared to oseltamivir carboxylate. Therefore, it is considered a promising lead compound for further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Chiara Bertagnin, Lorenzo Messa, Matteo Pavan, Marta Celegato, Mattia Sturlese, Beatrice Mercorelli, Stefano Moro, Arianna Loregian
Summary: HPV-induced cancers are a major global health issue and lack specific therapeutic regimens. In this study, researchers identified a compound that could inhibit the interaction between the E7 protein and PTPN14, leading to a reduction in viability, proliferation, migration, and cancer-stem cell potential of HPV-positive cervical cancer cells. This compound also showed activity against cervical cancer cells transformed by different high-risk HPV genotypes, suggesting a potential broad-spectrum activity.
