Article
Biology
Justin W. Flatt, Ausra Domanska, Alma L. Seppala, Sarah J. Butcher
Summary: Enteroviruses present a persistent and widespread threat to human physical health, with no specific treatments currently available. Small molecule capsid binders have the potential to be developed as antivirals to prevent virus attachment and entry into host cells. Structures of coxsackieviruses B3 and B4 bound to different capsid binders have been reported using single-particle cryo-EM, revealing detailed interactions and conserved virion-stabilizing networks at the interprotomer site.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Mathilde Briday, Francois Halle, Lauriane Lecoq, Sylvie Radix, Juliette Martin, Roland Montserret, Marie Dujardin, Marie-Laure Fogeron, Michael Nassal, Beat H. Meier, Thierry Lomberget, Anja Bockmann
Summary: Hepatitis B virus (HBV) is a significant human pathogen and its capsid-forming core protein (Cp) plays a key role in envelopment. Recent studies have found that Triton X-100, a detergent used in Cp purification, strongly binds to the hydrophobic pocket of Cp. The aromatic moiety is crucial for binding, while the aliphatic chain affects binding affinity. Moreover, the hydrophilic tail shows high tolerance to changes in length and type.
Article
Multidisciplinary Sciences
Lauriane Lecoq, Shishan Wang, Marie Dujardin, Peter Zimmermann, Leonard Schuster, Marie-Laure Fogeron, Mathilde Briday, Maarten Schledorn, Thomas Wiegand, Laura Cole, Roland Montserret, Stephane Bressanelli, Beat H. Meier, Michael Nassal, Anja Bockmann
Summary: A specific high-affinity pocket factor can trigger a conformational change in the capsid of hepatitis B virus, similar to a maturation signal. This interaction leads to the formulation of a synergistic double interaction hypothesis, providing a new concept for therapeutic interference with HBV envelopment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Virology
Anna Zimina, Ekaterina G. Viktorova, Seyedehmahsa Moghimi, Jules Nchoutmboube, George A. Belov
Summary: Through our study on poliovirus, we found that the capsid protein VP0 interacts with the cellular autophagy protein LC3A, while VP0 and P1 proteins strongly colocalize with the autophagy marker p62/SQSTM1. Furthermore, our research indicates that there is a specific autophagy response during infection, with the capsid proteins possibly being targeted to p62/SQSTM1-dependent sequestration in order to control viral protein levels and prevent premature removal of viral RNAs from the replication/translation pool.
Article
Biochemistry & Molecular Biology
Pavinee Prapassornwattana, Supa Hannongbua, Patchreenart Saparpakorn
Summary: This study reported the inhibitory activity of a benzene sulfonamide derivative against Coxsackievirus B3. By using molecular dynamics simulations and density functional theory, the key interactions between the compound and the viral capsid were investigated, and the differences in inhibitory activity against different mutants were explained. These findings are important for the development of drugs against CVB3.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Mukund M. G. Sudharsan, Rupesh Chikhale, Padma P. Nanaware, Somavally Dalvi, Prasanna Venkatraman
Summary: The study identified Doxorubicin as the first-generation small molecule inhibitor of PSMD10Gankyrin, with EEVD peptide, CLIC1, and Doxorubicin binding primarily to K116 and to a lesser extent R41 on PSMD10Gankyrin. These findings provide a chemical scaffold for designing novel inhibitors of PSMD10Gankyrin and will impact the field of protein interactions in disease biology and drug discovery.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sai Shi, Biao Ma, Qiushuang Ji, Shuai Guo, Hailong An, Sheng Ye
Summary: Researchers have discovered that the open state of the calcium-activated TMEM16A channel can be targeted by drugs to treat hypertension, secretory diarrhea, and various cancers. By using simulations and experiments, they identified a druggable pocket in the open state and found a potent inhibitor. The inhibitor was shown to inhibit prostate cancer cell proliferation, providing important insights for the design of novel inhibitors in chloride channel biology, biophysics, and medicinal chemistry.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Microbiology
Travis Chia, Tomofumi Nakamura, Masayuki Amano, Nobutoki Takamune, Masao Matsuoka, Hirotomo Nakata
Summary: ACAi-028, a small molecule identified through in vitro screening, inhibits HIV-1 replication by targeting a hydrophobic pocket in the N-terminal domain of the HIV-1 capsid. It interacts with specific amino acid residues in the CA-NTD pocket, demonstrating anti-HIV-1 activity by affecting core disassembly and stability. These findings suggest ACAi-028 as a promising CA inhibitor for HIV-1 treatment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Medicinal
Francisco Javier Luque, Maria-Jose Camarasa
Summary: This study identifies several fusion inhibitors targeting the membrane-proximal external region (MPER) of HIV-1 envelope spikes, revealing MPER as a new druggable target for anti-HIV-1 inhibitors. The compounds prevent the conformational changes necessary for membrane fusion, paving the way for novel therapeutic strategies against HIV-1 and other infectious diseases.
Article
Biochemistry & Molecular Biology
Sai Shi, Biao Ma, Fude Sun, Chang Qu, Hailong An
Summary: The study identified a highly effective TMEM16A inhibitor, theaflavin, which adopts a wedge insertion mode to block the ion conduction pore and induce pore closure. The experimental results confirmed the mechanism through which theaflavin binds to the specific binding pocket on TMEM16A, showing potential inhibitory effects on the growth and migration of lung adenocarcinoma cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Virology
Xiangyi Jiang, Prem Prakash Sharma, Brijesh Rathi, Xiangkai Ji, Lide Hu, Zhen Gao, Dongwei Kang, Zhao Wang, Minghui Xie, Shujing Xu, Xujie Zhang, Erik De Clercq, Simon Cocklin, Christophe Pannecouque, Alexej Dick, Xinyong Liu, Peng Zhan
Summary: Researchers have designed a series of novel 1,2,4-triazole phenylalanine derivatives using a scaffold hopping strategy. Compound d19, one of the derivatives, shows excellent antiretroviral potency against HIV-1 and HIV-2 strains and preferential interaction with the hexameric form of HIV-1 capsid protein. The study also provides insights into the binding mode and improved affinity and potency of d19 compared to PF-74.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Review
Oncology
Pier Francesco Ferrucci, Emilia Cocorocchio
Summary: Immunotherapy and targeted therapy have significantly changed the treatment landscape for melanoma, leading to long-term survival for many patients. However, a substantial portion of patients do not benefit from these innovative therapies, highlighting the need for affordable and reliable biomarkers to personalize treatment strategies.
Article
Chemistry, Medicinal
Nicole L. Inniss, Jan Kozic, Fengling Li, Monica Rosas-Lemus, George Minasov, Jiri Rybacek, Yingjie Zhu, Radek Pohl, Ludmilla Shuvalova, Lubomir Rulisek, Joseph S. Brunzelle, Lucie Bednarova, Milan Stefek, Jan Michael Kormanik, Erik Andris, Jaroslav Sebestik, Alice Shi Ming Li, Peter J. Brown, Uli Schmitz, Kumar Saikatendu, Edcon Chang, Radim Nencka, Masoud Vedadi, Karla J. F. Satchell
Summary: A collaborative, open-science team has discovered novel small molecule inhibitors of the SARS-CoV-2 nsp16-nsp10 2'-O-methyltransferase using a high throughput screening approach, revealing the druggability of a previously unrecognized cryptic pocket. This discovery provides new tools and suggests a new approach for the development of pan-coronavirus therapeutics based on nsp16 inhibition through structure-guided drug design.
ACS INFECTIOUS DISEASES
(2023)
Article
Virology
Manasi Majumdar, Cristina Celma, Elaine Pegg, Krunal Polra, Jake Dunning, Javier Martin
Summary: The study focused on a detection method for enteroviruses using NGS analysis of clinical samples, showing high concordance with conventional Sanger sequencing and good sensitivity and specificity for different EV types. The NGS method identified previously untyped EVs and potential co-infections, demonstrating its potential for comprehensive EV detection and genetic analysis.
Article
Cardiac & Cardiovascular Systems
Michael Wierer, Julia Werner, Jana Wobst, Adnan Kastrati, Ganildo Cepele, Redouane Aherrahrou, Hendrik B. Sager, Jeanette Erdmann, Martin Dichgans, Veit Flockerzi, Mete Civelek, Alexander Dietrich, Matthias Mann, Heribert Schunkert, Thorsten Kessler
Summary: Coronary in-stent restenosis is a complication with high morbidity and mortality rates. This study identified TRPC6 as a potential target for preventing neointima formation after vascular injury and stent implantation, based on proteomic analysis and genetic variant associations.
EUROPEAN HEART JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Winston Chiu, Joost Schepers, Thibault Francken, Laura Vangeel, Kayvan Abbasi, Dirk Jochmans, Steven De Jonghe, Hendrik Jan Thibaut, Volker Thiel, Johan Neyts, Manon Laporte, Pieter Leyssen
Summary: We developed a high-throughput screening method for antiviral drugs against SARS-CoV-2 using a fully automated robot system. This novel dual-reporter virus-cell-based imaging assay proved to be convenient and powerful for screening large compound libraries. The selected host cell subclone showed high expression of the reporter virus, resistance to virus-induced cytopathogenic effects, and strong fluorescent signals, making it suitable for high-throughput screening purposes.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Venkatesan Jayaprakash, Thangavelu Saravanan, Karuppaiyan Ravindran, Thangavelu Prabha, Jubie Selvaraj, Sudeepan Jayapalan, M. V. N. L. Chaitanya, Thangavel Sivakumar
Summary: In this study, a new open-source data analysis Python script was used to discover lead compounds for anticancer drugs by building a QSAR model using 53 thiazole derivatives. Machine learning approaches were employed, and the performance of the model was evaluated using three different algorithms.
CURRENT COMPUTER-AIDED DRUG DESIGN
(2023)
Article
Chemistry, Medicinal
Martina Salerno, Carmine Varricchio, Federica Bevilacqua, Dirk Jochmans, Johan Neyts, Andrea Brancale, Salvatore Ferla, Marcella Bassetto
Summary: Different viruses, such as enterovirus 71, rely on the host enzyme METTL3 to complete their cytoplasmic life cycle stages. By modulating the activity of this enzyme, it is possible to interfere with a broad range of viral infections. In this study, a series of nucleoside analogues were designed as inhibitors of human METTL3 to target multiple viral infections. Through molecular docking studies and synthesis, several novel and potent inhibitors of enterovirus 71 were identified.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Microbiology
Dirk Jochmans, Manon Laporte, Johan Neyts
Summary: Broad-spectrum antiviral drugs should be developed and stockpiled during epidemic/pandemic periods for immediate response to new virus outbreaks, and they will continue to be important tools even after the introduction of vaccines and monoclonal antibodies.
CELL HOST & MICROBE
(2023)
Article
Chemistry, Medicinal
Antonio Laghezza, Carmen Cerchia, Massimo Genovese, Rosalba Leuci, Erica Pranzini, Alice Santi, Leonardo Brunetti, Luca Piemontese, Paolo Tortorella, Abanish Biswas, Ravi Pratap Singh, Suhas Tambe, Sudeep Ca, Ashok Kumar Pattnaik, Venkatesan Jayaprakash, Paolo Paoli, Antonio Lavecchia, Fulvio Loiodice
Summary: A new ligand 10 was identified, which can potently activate both PPAR alpha and -gamma subtypes as full and partial agonists, respectively. Docking studies were performed to explain the different effects on the two targets. In vivo experiments showed that compound 10 significantly reduced blood glucose and lipid levels in diabetic mouse models without toxic effects, and further investigation revealed its inhibitory effect on the mitochondrial pyruvate carrier, suggesting its potential for treating dyslipidemic type 2 diabetes as a new class of drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Correction
Multidisciplinary Sciences
Emiel Michiels, Kenny Roose, Rodrigo Gallardo, Ladan Khodaparast, Laleh Khodaparast, Rob van der Kant, Maxime Siemons, Bert Houben, Meine Ramakers, Hannah Wilkinson, Patricia Guerreiro, Nikolaos Louros, Suzanne J. F. Kaptein, Lorena Itati Ibanez, Anouk Smet, Pieter Baatsen, Shu Liu, Ina Vorberg, Guy Bormans, Johan Neyts, Xavier Saelens, Frederic Rousseau, Joost Schymkowitz
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Rana Abdelnabi, Dirk Jochmans, Kim Donckers, Bettina Trueeb, Nadine Ebert, Birgit Weynand, Volker Thiel, Johan Neyts
Summary: The SARS-CoV-2 main protease (3CLpro) is an important target for COVID-19 treatment. A drug-resistant virus (3CLpro(res)) that is cross-resistant with nirmatrelvir has been identified. The 3CLpro(res) virus can replicate efficiently and be transmitted in Syrian hamsters, but nirmatrelvir still exhibits some antiviral activity against this virus.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Johan Neyts, Christophe Pannecouque, Tom Vermeyen, Wouter A. Herrebout, Luc Pieters, Emmy Tuenter
Summary: Scadoxus multiflorus is traditionally used for respiratory problems and this study investigated its alkaloidal composition. A previously undescribed alkaloid and fourteen known ones were identified. Some of the alkaloids exhibited weak antiviral activity against SARS-CoV-2, highlighting the potential of S. multiflorus as a source for anti-SARS-CoV-2 Amaryllidaceae alkaloid scaffolds.
PHYTOCHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Sayanti Halder, Abhishek Thakur, Supriya Suman Keshry, Pradip Jana, Divyanshi Karothia, Indrani Das Jana, Orlando Acevedo, Rajeeb K. Swain, Arindam Mondal, Soma Chattopadhyay, Venkatesan Jayaprakash, Abhimanyu Dev
Summary: The article introduces an aptamer-based system with diagnostic and therapeutic potential against COVID-19. Aptamer R is shown to specifically inhibit the entry of SARS-CoV-2 virus, and its antiviral potential is tested and analyzed. The study also investigates the intermolecular interactions between the aptamers and the virus domain.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Rana Abdelnabi, Patricia Perez, David Astorgano, Guillermo Albericio, Winnie Kerstens, Hendrik Jan Thibaut, Lotte Coelmont, Birgit Weynand, Nuria Labiod, Rafael Delgado, Dolores Montenegro, Eugenia Puentes, Esteban Rodriguez, Johan Neyts, Kai Dallmeier, Mariano Esteban, Juan Garcia-Arriaza
Summary: This study describes the enhanced immunogenicity and efficacy of the MVA-S(3P) vaccine in hamsters. Vaccinated hamsters developed high titers of antibodies that could neutralize different variants of the virus and showed reduced disease symptoms after infection. Additionally, the vaccine reduced lung pathology and proinflammatory cytokine levels.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Sirle Saul, Kathleen E. Huie, Courtney Tindle, Mamdouh Sibai, Chengjin Ye, Ahmed Magdy Khalil, Kevin Chiem, Luis Martinez-Sobrido, John M. Dye, Benjamin A. Pinsky, Pradipta Ghosh, Soumita Das, David E. Solow-Cordero, Jing Jin, John P. Wikswo, Dirk Jochmans, Johan Neyts, Steven De Jonghe, Aarthi Narayanan, Shirit Einav, Marwah Karim, Luca Ghita, Pei-Tzu Huang, Winston Chiu, Veronica Duran, Chieh-Wen Lo, Sathish Kumar, Nishank Bhalla, Pieter Leyssen, Farhang Alem, Niloufar A. Boghdeh, Do H. N. Tran, Courtney A. Cohen, Jacquelyn A. Brown
Summary: Targeting host factors exploited by multiple viruses could provide a broad solution for pandemic preparedness. In a compound screen, lapatinib and other ErbB inhibitors were identified as effective against SARS-CoV-2 and other emerging viruses. Lapatinib acts by suppressing viral entry and later stages of the viral life cycle and shows synergy with direct-acting antivirals. It also protects against lung injury, inflammation, and blood-brain barrier disruption caused by SARS-CoV-2 and other viruses.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Plant Sciences
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Johan Neyts, Christophe Pannecouque, Tom Vermeyen, Wouter A. Herrebout, Luc Pieters, Emmy Tuenter
Summary: A new alkaloid, along with 17 known alkaloids, was isolated and identified from Pancratium maritimum using advanced probabilistic methods and spectroscopic techniques. Assessment of their anti-SARS-CoV-2 activity and cytotoxicity revealed several compounds with weak antiviral potency at non-toxic concentrations, while some compounds showed cytotoxicity.
PHYTOCHEMISTRY LETTERS
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Zhenzhen Shi, Xin Zhang, Niels Cremers, Johan Neyts, Harel Dahari, Suzanne Kaptein
JOURNAL OF HEPATOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Kalliopi Pervolaraki, Jean-Christophe Vanherck, Charlene Marcadet, Lieven Verhoye, Amse De Meyer, Madina Rasulova, Heyrhyoung Lyoo, Jasmine Paulissen, Hendrik Jan Thibaut, Kristof De Vos, Patrick Chaltin, Johan Neyts, Pieter Annaert, Philip Meuleman, Arnaud Marchand, Matthias Versele, Stan van de Graaf
JOURNAL OF HEPATOLOGY
(2023)
