Article
Multidisciplinary Sciences
Takao Morimune, Ayami Tano, Yuya Tanaka, Haruka Yukiue, Takefumi Yamamoto, Ikuo Tooyama, Yoshihiro Maruo, Masaki Nishimura, Masaki Mori
Summary: Research has shown that the protein Tbc1d24 forms unique cellular structures called cytoophidia in neuronal cells, which are different from other types of cytoophidia. The formation of Tbc1d24 cytoophidia is influenced by cellular juvenescence and affects its enzymatic activity.
Article
Chemistry, Organic
Xin Liu, Yan Fu, Qiqi Zhou, Su Wang, Lu Gao, Jiali Lei, Aibing Ke, Yeying Li, Xuexia Zhang, Changhong Huo, Xinhua Lu
Summary: Five unprecedented chromone derivatives were obtained from the fungus Aspergillus deflectus NCC0415, and their structures were identified using various techniques. The hexacyclic derivatives showed potent enzyme inhibition activity.
Article
Multidisciplinary Sciences
Kathleen A. Cashman, Eric R. Wilkinson, Jeffrey Posakony, Ikenna G. Madu, Eric J. Tarcha, Kurt H. Lustig, Marcus J. Korth, Kristin M. Bedard, Sean M. Amberg
Summary: LHF-535, a small molecule antiviral, shows promising results in reducing viremia and clinical signs in a guinea pig model of Lassa fever, and protects animals from death. Further development of LHF-535 as a therapeutic for Lassa fever is supported by its pharmacokinetics.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Ling-Jie Gao, Yuan Lin, Steven De Jonghe, Mark Waer, Piet Herdewijn
Summary: Researchers prepared three different types of prodrugs of Mizoribine, and found that the ester derivatives effectively inhibited the secretion of specific immune molecules and prolonged graft survival. The combination therapy of these prodrugs with tacrolimus also showed a synergistic effect in vivo.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biology
Nicolas Baillet, Stephanie Reynard, Emeline Perthame, Jimmy Hortion, Alexandra Journeaux, Mathieu Mateo, Xavier Carnec, Justine Schaeffer, Caroline Picard, Laura Barrot, Stephane Barron, Audrey Vallve, Aurelie Duthey, Frederic Jacquot, Cathy Boehringer, Gregory Jouvion, Natalia Pietrosemoli, Rachel Legendre, Marie-Agnes Dillies, Richard Allan, Catherine Legras-Lachuer, Caroline Carbonnelle, Herve Raoul, Sylvain Baize
Summary: This study used a cynomolgus monkey model to replicate Lassa virus and associated Lassa fever, finding that in fatal cases of the disease there is a decrease in T-cell responses leading to systemic viral dissemination and multiorgan failure. The results suggest that the outcome of Lassa fever may be determined early after infection, which could help in the development of early diagnostic tools.
COMMUNICATIONS BIOLOGY
(2021)
Letter
Clinical Neurology
Pin-Shiuan Chen, Meng-Chen Wu, Chun-Hwei Tai, Yung-Yee Chang, Min-Yu Lan, Ying-Fa Chen, Han- Lin, Ni-Chung Lee, Chin-Hsien Lin
Summary: We investigated 245 Taiwanese patients with dystonia and found no evidence to suggest a link between the inosine monophosphate dehydrogenase gene (IMPDH2) and the disease, suggesting that IMPDH2 may not play a major role in dystonia.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Marianna Lovaszi, Zoltan H. Nemeth, William C. Gause, Jennet Beesley, Pal Pacher, Gyorgy Hasko
Summary: The study demonstrates that IMP can regulate inflammation through metabolism to inosine, which may be beneficial for treating certain diseases clinically.
Review
Immunology
Hannah Murphy, Hinh Ly
Summary: In this article, we provide a literature review on the current understanding of the basic mechanism of immune responses to LASV infection in animal models and patients, as well as several candidate vaccines.
Article
Multidisciplinary Sciences
Michael Katz, Jonathan Weinstein, Maayan Eilon-Ashkenazy, Katrin Gehring, Hadas Cohen-Dvashi, Nadav Elad, Sarel J. Fleishman, Ron Diskin
Summary: Lassa virus, a human pathogen, has a spike complex on its surface that facilitates cell entry. The structure of the spike complex reveals the role of the signal peptide in stabilizing the complex and provides insights into the mechanism of binding with the host cell.
Article
Oncology
Shiyu Wang, Fan Chao, Cong Zhang, Dunsheng Han, Guoxiong Xu, Gang Chen
Summary: The study found that circPFKP was significantly increased in prostate cancer tissues compared to noncancerous tissues, and was correlated with PCa risk classification, N stage, and prognostic group. CircPFKP promotes PCa cell proliferation by interacting with IMPDH2, and its production may be facilitated by hnRNPF binding.
Article
Virology
Toru Takenaga, Zihan Zhang, Yukiko Muramoto, Sarah Katharina Fehling, Ai Hirabayashi, Yuki Takamatsu, Junichi Kajikawa, Sho Miyamoto, Masahiro Nakano, Shuzo Urata, Allison Groseth, Thomas Strecker, Takeshi Noda
Summary: The research identified CP100356 as an effective virus entry inhibitor, capable of suppressing LASV and other highly pathogenic mammarenavirus infections with low half maximal inhibitory concentrations and without cytotoxicity.
Article
Biochemical Research Methods
Guillaume Lingas, Kyle Rosenke, David Safronetz, Jeremie Guedj
Summary: Lassa fever is caused by Lassa virus and currently has no approved vaccine. Recent findings show that the nucleotide analogue favipiravir has a high antiviral efficacy against Lassa virus, but its mechanism of action is not clear and the lack of pharmacokinetic data hinders the translation of these results to humans.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Yun Wang, Tianqing Xia, Chenhao Li, Duwen Zeng, Lili Xu, Liyun Song, Hengsong Yu, Shichao Chen, Jianzhi Zhao, Xiaoming Bao
Summary: Saccharomyces cerevisiae has been identified as a preferred source for industrial production of ribonucleic acids (RNAs) and their derivatives. In this study, a modified RNA polymerase I-mediated green fluorescent protein expression system was used to screen and identify an industrial S. cerevisiae strain with an 18.2% increase in RNA content. Transcriptome analysis showed enhanced activity of genes and pathways associated with rRNA transcription, purine metabolism, and phosphate transport. The study provides valuable insights into RNA synthesis and its application in the food industry.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Immunology
Stephen R. Welch, Sarah C. Genzer, Joann D. Coleman-McCray, Jessica R. Harmon, Florine E. M. Scholte, Joel M. Montgomery, Christina F. Spiropoulou, Jessica R. Spengler
Summary: Lassa fever, caused by Lassa virus, is a localized disease endemic to West Africa. This study found that viral RNA and infectious virus can be detected in various specimen types, with conjunctival and nasal specimens yielding the highest amount of infectious virus. These findings suggest the risk of mucosal transmission and highlight the potential utility of RT-qPCR for LASV diagnostics.
EMERGING MICROBES & INFECTIONS
(2022)
Review
Public, Environmental & Occupational Health
Oluwafemi O. Balogun, Oluwatosin W. Akande, Davidson H. Hamer
Summary: Lassa fever is endemic in parts of West Africa and remains a global threat. This review provides a comprehensive overview of the disease's background, factors contributing to its emergence and spread, preventive measures, and potential solutions, serving as a valuable resource for various stakeholders.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(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
Pharmacology & Pharmacy
Olivia Goethals, Natalia V. Voge, Bart Kesteleyn, Patrick Chaltin, Tim Jinks, Tine De Marez, Anil Koul, Ruxandra Draghia-Akli, Johan Neyts, Marnix Van Loock
Summary: Despite some progress, there are still unmet medical needs for neglected tropical diseases. The World Health Organization encourages public-private partnerships to address this issue. Pharmaceutical companies are contributing to research efforts in different ways. This review illustrates the role of a public-private partnership in the research and development of a dengue antiviral molecule.
ANTIVIRAL RESEARCH
(2023)
Article
Virology
Gilda Giancotti, Giulio Nannetti, Gilda Padalino, Martina Landini, Nanci Santos-Ferreira, Jana Van Dycke, Valentina Naccarato, Usheer Patel, Romano Silvestri, Johan Neyts, Roberto Gozalbo-Rovira, Jesus Rodriguez-Diaz, Joana Rocha-Pereira, Andrea Brancale, Salvatore Ferla, Marcella Bassetto
Summary: Human norovirus is the leading cause of foodborne diseases worldwide, resulting in severe acute gastroenteritis outbreaks and causing approximately 200,000 deaths in children in developing countries annually. Current treatment options are limited to supportive care, highlighting the urgent need for antiviral agents. In this study, we focused on the viral RNA-dependent RNA polymerase (RdRp) as a potential target for antiviral drug discovery. By rationally modifying identified scaffolds, we synthesized new compounds with improved inhibition of RdRp, providing a promising foundation for further optimization.
Article
Chemistry, Multidisciplinary
Roeland Vanhoutte, Marta Barniol-Xicota, Winston Chiu, Laura Vangeel, Dirk Jochmans, Steven De Jonghe, Hadeer Zidane, Haim M. Barr, Nir London, Johan Neyts, Steven H. L. Verhelst
Summary: The vulnerability of the modern society has been exposed by the COVID-19 pandemic, and it is crucial to have effective treatment options for infected individuals. We have designed a solid-phase synthesis route to create azapeptide activity-based probes for the SARS-CoV-2 main protease, which have shown to be potent inhibitors. These probes can be used to visualize the activity of the protease and the engagement of drugs in infected cells.
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
Biochemistry & Molecular Biology
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Tom Vermeyen, Aliou M. Balde, Wouter A. Herrebout, Johan Neyts, Christophe Pannecouque, Luc Pieters, Emmy Tuenter
Summary: This study investigated the bioactive constituents of Hymenocallis littoralis and identified three previously undescribed compounds, as well as six known compounds. Some of these compounds showed weak inhibitory activity against SARS-CoV-2 at non-cytotoxic concentrations. Furthermore, a preliminary structure-activity relationship for lycorine-type alkaloids in anti-SARS-CoV-2 activity was explored, suggesting the importance of ring C.
Article
Infectious Diseases
Nzelle Delphine Kayem, Sylvanus Okogbenin, Joseph Okoeguale, Joseph Eigbefoh, Joseph Ikheloa, Reuben Eifediyi, Xavier Enodiana, Olugbenga Emmanuel Olorogbogo, Isoken Aikpokpo, Yemisi Ighodalo, Thomas Olokor, George Odigie, Lyndsey Castle, Sophie Duraffour, Lisa Oestereich, Prabin Dahal, Proochista Ariana, Stephan Gunther, Peter Horby
Summary: This study aims to evaluate the efficiency of transplacental transfer of Lassa virus antibodies from mother to child. The study demonstrates that maternal antibody levels play a crucial role in determining the transfer efficiency and may be influenced by the timing of antibody development. The study suggests that vaccination before pregnancy, in women of childbearing age, may be more appropriate for protecting both pregnant women and their neonates.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Infectious Diseases
Nzelle Delphine Kayem, Sylvanus Okogbenin, Joseph Okoeguale, Mojeed Momoh, Antonia Njoku, Reuben Eifediyi, Xavier Enodiana, Hilary Ngwu, Wilfred Irhiogbe, Yemisi Ighodalo, Thomas Olokor, George Odigie, Lyndsey Castle, Sophie Duraffour, Lisa Oestereich, Prabin Dahal, Proochista Ariana, Stephan Gunther, Peter Horby
Summary: This study evaluated the epidemiology of Lassa fever in pregnant women in South Nigeria and found that about 50% of pregnant women had Lassa virus antibodies, indicating a high risk of Lassa infection during pregnancy. It also suggested that 35.0% of infections could be prevented by avoiding rodent exposure and conditions that facilitate infestation. Public health measures such as improved sanitation and hygiene could be beneficial in reducing the risk of infection.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
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
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
Viktor Lemmens, Lara Kelchtermans, Sarah Debaveye, Winston Chiu, Thomas Vercruysse, Ji Ma, Hendrik Jan Thibaut, Johan Neyts, Lorena Sanchez-Felipe, Kai Dallmeier
Summary: A new vaccine candidate called YF-EBO, based on the live vaccine YF17D, has been developed to combat Ebola virus. YF-EBO not only provides protection against Ebola, but also against yellow fever. It has been shown to be safe and effective in mouse models, inducing high levels of antibodies and cellular immune responses.
Article
Cell Biology
Lize Cuypers, Els Keyaerts, Samuel Leandro Hong, Sarah Gorissen, Soraya Maria Menezes, Marick Starick, Jan Van Elslande, Matthias Weemaes, Tony Wawina-Bokalanga, Joan Marti-Carreras, Bert Vanmechelen, Bram Van Holm, Mandy Bloemen, Jean-Michel Dogne, Francois Dufrasne, Keith Durkin, Jean Ruelle, Ricardo De Mendonca, Elke Wollants, Pieter Vermeersch, Caroline Boulouffe, Achille Djiena, Caroline Broucke, Boudewijn Catry, Katrien Lagrou, Marc Van Ranst, Johan Neyts, Guy Baele, Piet Maes, Emmanuel Andre, Simon Dellicour, Johan Van Weyenbergh
