Editorial Material
Microbiology
David Aponte-Diaz, Matthew R. Vogt, Craig E. Cameron
Summary: EV-D68 contributes significantly to respiratory and neurological diseases. It exploits cellular autophagic compartments and its viral proteins 2B and 3A have difficulty engaging membranes, leading to a delay in RNA synthesis.
Article
Virology
Luca Murer, Anthony Petkidis, Thomas Vallet, Marco Vignuzzi, Urs F. Greber
Summary: The study reveals that by altering viral proteins, the virus can develop drug resistance, providing a deeper understanding of the drug resistance mechanisms against low pH in endolysosomes. This opens up new avenues for using endosomal acidification inhibitors as a strategy against RVs, especially if directly applied to the airways.
JOURNAL OF VIROLOGY
(2022)
Article
Cell Biology
Marie N. Sorin, Antonio Di Maio, Lisete M. Silva, Domenic Ebert, Clement P. Delannoy, Ngoc-Khan Nguyen, Yann Guerardel, Wengang Chai, Franck Halary, Karine Renaudin-Autain, Yan Liu, Celine Bressollette-Bodin, Thilo Stehle, Dorian McIlroy
Summary: This study characterizes the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism in BK polyomavirus (BKPyV). Mutants E73Q, E73A, and A72V-E73Q-E82Q (VQQ) retain sialic acid-dependent infectious entry and bind to a-series gangliosides, including GD1a. However, E73A and VQQ mutants lose the ability to infect ganglioside-complemented cells, and this correlates with a BC2 loop shift in their crystal structures. The K69N mutation in the K69N-E82Q variant inhibits sialic acid binding but retains significant infectivity in 293TT cells, suggesting the existence of an unknown sialic acid-independent entry receptor for BKPyV.
Article
Biology
Florian Mattenberger, Victor Latorre, Omer Tirosh, Adi Stern, Ron Geller
Summary: This study comprehensively defines the effects of mutations on the capsid of a human picornavirus, identifying key structural and sequence determinants that predict mutational fitness effects. It also introduces a bioinformatic approach for identifying host proteins targeted by viral proteases based on capsid-encoded protease cleavage sites, shedding light on important aspects of viral biology, evolution, and host interactions.
Article
Biology
Jessica Swanson, Rennos Fragkoudis, Philippa C. Hawes, Joseph Newman, Alison Burman, Anusha Panjwani, Nicola J. Stonehouse, Tobias J. Tuthill
Summary: This study successfully displayed the N-terminal epitope of FMDV VP4 using HBc VLPs. The research found that inserting VP4 into the spike induced VP4-specific antibodies, while attaching VP4 peptides to the spikes did not.
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
Virology
Yilin Deng, Taojun He, Bin Li, Hanmei Yuan, Fang Zhang, Hui Wu, Jie Ning, Yanping Zhang, Aixia Zhai, Chao Wu
Summary: This study describes the specific antibody responses of VP2 and identifies its B-cell epitopes for the first time. The findings provide data for a more thorough understanding of norovirus capsid protein-specific IgG responses and could be useful for designing and developing vaccines.
Article
Multidisciplinary Sciences
Karel Skubnik, Lukas Sukenik, David Buchta, Tibor Fuzik, Michaela Prochazkova, Jana Moravcova, Lenka Smerdova, Antonin Pridal, Robert Vacha, Pavel Plevka
Summary: The Iflaviridae family consists of economically important viruses affecting western honeybees. These viruses induce genome release through conformational changes triggered by acidic pH, with different mechanisms for releasing genomes from their capsids.
Article
Biotechnology & Applied Microbiology
Anshu Nain, Mohit Kumar, Manidipa Banerjee
Summary: This study successfully generated recombinant VP1 oligomers from Hepatitis A Virus in the E. coli expression system. Purification of the protein from inclusion bodies and refolding resulted in correctly folded VP1 oligomers with similar structure to other picornaviruses. These VP1 oligomers could be utilized for understanding the molecular pathway of HAV capsid assembly and have potential biomedical applications in prevention and diagnostics of HAV infections.
MICROBIAL CELL FACTORIES
(2022)
Article
Multidisciplinary Sciences
Yong Wah Tan, Wan Keat Yam, Rachel Jia Wen Kooi, Jacob Westman, Gustav Arbrandt, Justin Jang Hann Chu
Summary: Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness that has become a significant public health threat in recent years, especially in the Asia-Pacific region. Infections by Enterovirus A71 (EV-A71) are associated with severe disease, but there is currently no effective antiviral treatment for EV-A71 infections. However, research has shown that certain antiviral compounds can significantly improve survival and pathology of infected mice, particularly when used in combination.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Nadezda Pupina, Annela Avarlaid, Helle Sadam, Arno Pihlak, Mariliis Jaago, Jurgen Tuvikene, Annika Rahni, Anu Planken, Margus Planken, Eija Kalso, Pentti J. Tienari, Janne K. Nieminen, Mikko R. J. Seppanen, Antti Vaheri, Dan Lindholm, Juha Sinisalo, Pirkko Pussinen, Tonis Timmusk, Kaia Palm
Summary: This study investigates the association between antibody-based immune response and severe cardiovascular conditions. The findings suggest that antibody response to the G-I-X-D epitope is associated with polio vaccinations. Low levels of antibody response to this epitope may be linked to severe cardiac disease complications.
Article
Biology
Joseph Newman, David J. Rowlands, Tobias J. Tuthill
Summary: This study compared the characteristics of recombinant assembly and disassembly pentamers of picornavirus, specifically FMDV. Assembly pentamers sedimented faster and had higher reactivity with anti-VP4 antibodies compared to the disassembly pentamers. However, the reactivity with other antibodies was similar between the two pentamers, suggesting that major antigenic features may be preserved between assembly pentamers containing VP4 and disassembly pentamers lacking VP4.
Article
Virology
Dennis S. Winston, David D. Boehr
Summary: Viruses have evolved strategies to maximize genetic material usage, including proteolytic cleavage of polyproteins for different functions. Studies show that 3CD has different protease specificity and conformational dynamics compared to 3C and 3D. This may allow 3CD to perform additional functions despite having similar lowest-energy structures to 3C and 3D.
Article
Virology
Mary Bridget Nanteza, Barnabas Bakamutumaho, Phionah Tushabe, Prossy Namuwulya, Molly Birungi, Rajab Dhatemwa, James Peter Eliku, Mayi Tibanagwa, Proscovia Kakooza, Henry Bukenya, Josephine Bwogi, Charles Rutebarika Byabamazima
Summary: Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine that can lead to outbreaks and permanent disability. Understanding the evolution of the polio virus protein 1 (VP1) among AFP patients could provide valuable insights into the development of vaccine-derived polioviruses. Mutations in VP1, such as T106A and A54V, were common among AFP patients, along with other substitutions and nucleotide mutations. Characterizing these mutations could help mitigate the risk of vaccine-derived polioviruses and improve vaccine safety.
Article
Biology
Carina R. Buettner, Radovan Spurny, Tibor Fuezik, Pavel Plevka
Summary: CV-A6 has become the primary causative agent of hand, foot, and mouth disease worldwide. Unlike other enteroviruses, CV-A6 uses altered particles to infect cells. The structure of CV-A6 virion is similar to other enteroviruses and plays a crucial role in infection.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Saida Lachhab, Az-eddine El Mansouri, Ahmad Mehdi, Indira Dennemont, Johan Neyts, Dirk Jochmans, Graciela Andrei, Robert Snoeck, Yogesh S. Sanghvi, Mustapha Ait Ali, Philippe M. Loiseau, Hassan B. Lazrek
Summary: A new series of 3-acetyl-1,3,4-oxadiazoline hybrid molecules were designed and synthesized, and their activities against pathogens were screened. One of the intermediates exhibited significant antileishmanial activity.
MOLECULAR DIVERSITY
(2023)
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, Physical
Az-Eddine El Mansouri, Saida Lachhab, Ali Oubella, Mehdi Ahmad, Johan Neyts, Dirk Jochmans, Winston Chiu, Laura Vangeel, Steven De Jonghe, Hamid Morjani, Mustapha Ait Ali, Mohamed Zahouily, Yogesh S. Sanghvi, Hassan B. Lazrek
Summary: Analogous to pyrimidine and 1,3,4-oxadiazole, the newly synthesized pyrimidine-1,3,4-oxadiazole conjugated hybrid molecules exhibited potential anticancer activity. Specifically, compound 5e demonstrated significant growth inhibition against various cancer cell lines and induced apoptosis through caspase activation and cell-cycle arrest.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Shenghua Gao, Letian Song, Hongtao Xu, Antonios Fikatas, Merel Oeyen, Steven De Jonghe, Fabao Zhao, Lanlan Jing, Dirk Jochmans, Laura Vangeel, Yusen Cheng, Dongwei Kang, Johan Neyts, Piet Herdewijn, Dominique Schols, Peng Zhan, Xinyong Liu
Summary: DF-47 and DF-51 were identified as effective inhibitors of SARS-CoV-2/DENV polymerase through RdRp inhibition screening and in vitro antiviral study. In silico simulation revealed stable binding modes between DF-47/DF-51 and SARS-CoV-2/DENV RdRp, including chelating with Mg2+ near the polymerase active site. These polyphenols have the potential to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with a new scaffold.
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)
Editorial Material
Gastroenterology & Hepatology
Jerome Gouttenoire, Johan Neyts
Article
Biochemistry & Molecular Biology
Olaia Marti-Mari, Rana Abdelnabi, Dominique Schols, Johan Neyts, Maria-Jose Camarasa, Federico Gago, Ana San-Felix
Summary: AL-471 is a potent inhibitor of HIV and EV-A71 entry, and our research group has made further improvements on it. The antiviral activity of the compounds seems to be largely independent of the Trp stereochemistry and is dependent on both the Trp unit and the distal isophthalic moiety. One derivative, 23 (AL-534), with the shortest alkyl urea linkage, showed subnanomolar potency against different EV-71 clinical isolates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Elise Wouters, Caro Verbrugghe, Rana Abdelnabi, Rosalie Devloo, Dorien De Clippel, Dirk Jochmans, Dominique De Bleser, Birgit Weynand, Veerle Compernolle, Johan Neyts, Hendrik B. Feys
Summary: Convalescent plasma (CP) transfusion is an effective prophylactic for COVID-19, especially when administered within 5 days after symptom onset. Testing on hamsters showed that high-titer CP provided significant protection against viral infection. Therefore, including CP transfusion in future pandemic preparedness plans is crucial.
Article
Pharmacology & Pharmacy
Xinyu Wang, Lisanne Terrie, Guanghui Wu, Els J. M. Van Damme, Lieven Thorrez, Anthony R. Fooks, Ashley C. Banyard, Dirk Jochmans, Johan Neyts
Summary: Infection with the rabies virus is a deadly neurological disease, but post-exposure prophylaxis (PEP) with vaccination and anti-rabies immunoglobulins (RIGs) is 100% effective if administered early. This study found that Urtica dioica agglutinin (UDA), a specific lectin, can prevent the entry of the virus into host cells and effectively stop virus replication in a muscle model. UDA holds promise as a cheap and simple alternative for RIGs in PEP.
Article
Microbiology
Tatiana M. T. Rezende, Gabriella Macera, Leo Heyndrickx, Johan Michiels, Sandra Coppens, Hendrik Jan Thibaut, Kai Dallmeier, Marjan Van Esbroeck, Johan Neyts, Kevin K. Arien, Koen Bartholomeeusen
Summary: This article reports the validation of a new reporter cell line, Hec1a-IFNB-Luc, for the inhibition studies of various flaviviruses relevant to human pathology. The cell line showed high responsiveness to all tested flaviviruses, including dengue virus serotypes. It is comparable to clinically applied assays in measuring neutralizing antibody activity and assessing the antiviral activities of small-molecule compounds.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Jordi Doijen, Koen Temmerman, Christel van den Eynde, Annick Diels, Nick Van den Broeck, Michiel Van Gool, Inha Heo, Steffen Jaensch, Marleen Zwaagstra, Mayra Diosa Toro, Winston Chiu, Steven De Jonghe, Pieter Leyssen, Denisa Bojkova, Sandra Ciesek, Jindrich Cinatl, Lore Verschueren, Christophe Buyck, Frank Van Kuppeveld, Johan Neyts, Marnix Van Loock, Ellen Van Damme
Summary: This article reports the discovery of a small molecule, Z-Tyr-Ala-CHN2, which shows sub-micromolar antiviral activity against SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. The molecule acts at the early phase of the infection cycle by inhibiting cathepsin L. Although its activity is cell-specific, Z-Tyr-Ala-CHN2 can be a useful tool compound for studying the biology of coronavirus entry and replication.
Article
Pharmacology & Pharmacy
Xin Zhang, Niels Cremers, Stijn Hendrickx, Yannick Debing, Tania Roskams, Lotte Coelmont, Johan Neyts, Suzanne J. F. Kaptein
Summary: Hepatitis E virus (HEV) is a major cause of hepatitis, with an estimated 3.3 million symptomatic cases annually. Currently, there is no specific treatment for HEV, and a vaccine is only available in China and Pakistan. To aid in the development of therapeutic and preventive strategies, convenient HEV infection models in small laboratory animals are needed.
ANTIVIRAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Robert Konkel, Aleksandra Milewska, Nguyen Dan Thuc Do, Emilia Barreto Duran, Artur Szczepanski, Jacek Plewka, Ewa Wieczerzak, Sofia Iliakopoulou, Triantafyllos Kaloudis, Dirk Jochmans, Johan Neyts, Krzysztof Pyrc, Hanna Mazur-Marzec
Summary: In this study, fifteen cyanopeptolins (CPs) were isolated from the Baltic cyanobacterium Nostoc edaphicum and tested for their activity against SARS-CoV-2. The results showed that the Arg-containing CP978 exhibited the strongest inhibition of Delta SARS-CoV-2 infection, possibly through direct interaction with the virus. CP978 also showed significant reduction in virus replication in human airway epithelial cells. Among the tested SARS-CoV-2 variants, CP978 had no effect on the Wuhan variant. These findings suggest that CP978 has potential as an antiviral drug candidate.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Bart Kesteleyn, Dorotheie Bardiot, Jean-Francois Bonfanti, Benoit De Boeck, Olivia Goethals, Suzanne J. F. Kaptein, Bart Stoops, Erwin Coesemans, Jeirome Fortin, Philippe Muller, Freideiric Doublet, Gunter Carlens, Mohamed Koukni, Wim Smets, Pierre Raboisson, Patrick Chaltin, Kenny Simmen, Marnix Van Loock, Johan Neyts, Arnaud Marchand, Tim H. M. Jonckers
Summary: The discovery and development of a novel small-molecule antiviral for dengue prevention or treatment is critical due to the absence of approved dengue-specific treatment. This study identified a series of 3-acyl-indole derivatives as potent dengue virus inhibitors and optimized them to improve their effectiveness against all four DENV serotypes. The optimized candidates demonstrated good chiral stability, oral bioavailability, and efficacy in treating DENV-2 infection in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(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)