Article
Multidisciplinary Sciences
C. Garrett Rappazzo, Longping Tse, Chengzi Kaku, Daniel Wrapp, Mrunal Sakharkar, Deli Huang, Laura M. Deveau, Thomas J. Yockachonis, Andrew S. Herbert, Michael B. Battles, Cecilia M. O'Brien, Michael E. Brown, James C. Geoghegan, Jonathan Belk, Linghang Peng, Linlin Yang, Yixuan Hou, Trevor D. Scobey, Dennis R. Burton, David Nemazee, John M. Dye, James E. Voss, Bronwyn M. Gunn, Jason S. McLellan, Ralph S. Baric, Lisa E. Gralinski, Laura M. Walker
Summary: The engineered antibody ADG-2 shows enhanced neutralization breadth and potency against a wide range of sarbecoviruses, providing complete protection in SARS and COVID-19 mouse models. Structural and biochemical studies reveal that ADG-2 targets a highly conserved epitope through a unique angle of approach.
Article
Immunology
Sara Shokry, Akram Hegazy, Ahmad M. Abbas, Islam Mostafa, Ibrahim H. Eissa, Ahmed M. Metwaly, Galal Yahya, Assem M. El-Shazly, Khaled M. Aboshanab, Ahmed Mostafa
Summary: This study investigated the anti-influenza activity of various plant-derived phytochemicals against highly pathogenic avian influenza A/H5N1 virus and seasonal low pathogenic human influenza A/H1N1 virus. Among 22 tested phytochemicals, the steroid compounds beta-sitosterol and beta-sitosterol-O-glucoside showed potent activity against the predefined influenza viruses. These steroids could affect multiple stages of the influenza virus replication cycle and have a significant viricidal effect.
Article
Pharmacology & Pharmacy
Geraldine Nadya Putri, Chandra Sekhar Gudla, Mayas Singh, Chin Huan Ng, Fakhriedzwan Fitri Haji Idris, Yukei Oo, Jasmine Hwee Yee Tan, Joel Feng Jie Wong, Justin Jang Hann Chu, Vignesh Selvam, Siva Shanmugam Selvaraj, Radha Krishan Shandil, Shridhar Narayanan, Sylvie Alonso
Summary: With the lack of approved antiviral agents to effectively treat Dengue virus (DENV) infection, a study has developed a series of baicalein derivatives with improved antiviral activity. Compound 11064 emerged as a promising lead candidate, exhibiting antiviral activity against DENV and Zika virus in vitro. Mechanistic studies suggest that the compound targets the host rather than a viral protein, indicating its broad-spectrum antiviral potential.
ANTIVIRAL RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Peifen Wu, Jie Yang, Chi Chen, Ruili Li, Shunxian Chen, Yanlin Weng, Yayi Lin, Zhiying Chen, Fengfan Yu, Xucong Lu, Li Ni, Jinzhi Han
Summary: Infections caused by drug-resistant pathogens pose a significant challenge to wound healing. This study successfully designed a new antimicrobial peptide, AB7, through truncation, amino acid replacement, and heterozygosity, and found that it displayed broad-spectrum and potent antimicrobial activity against drug-resistant bacteria. Experimental results demonstrated that AB7 had good anti-infection ability in a MRSA-infected skin wound model and promoted wound healing and angiogenesis.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Han Dong, James Dongjoo Ham, Guangan Hu, Guozhu Xie, Juliana Vergara, Yong Liang, Alaa Ali, Mubin Tarannum, Hannah Donner, Joanna Baginska, Yasmin Abdulhamid, Khanhlinh Dinh, Robert J. Soiffer, Jerome Ritz, Laurie H. Glimcher, Jianzhu Chen, Rizwan Romee
Summary: Acute myeloid leukemia (AML) is difficult to treat due to a lack of tumor-specific targets for immune-based therapies. Recent studies have shown that natural killer (NK) cells exhibit innate memory and enhanced antitumor activity when activated with IL-12 and IL-18. This study demonstrates that arming CIML NK cells with a neoepitope-specific CAR significantly improves their antitumor responses to NPM1-mutated AML and avoids off-target toxicity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Han Dong, James Dongjoo Ham, Guangan Hu, Guozhu Xie, Juliana Vergara, Yong Liang, Alaa Ali, Mubin Tarannum, Hannah Donner, Joanna Baginska, Yasmin Abdulhamid, Khanhlinh Dinh, Robert J. Soiffer, Jerome Ritz, Laurie H. Glimcher, Jianzhu Chen, Rizwan Romee
Summary: Recent studies have shown that natural killer (NK) cells exhibit innate memory and enhanced antitumor activity upon activation with IL-12 and IL-18, providing a potential therapeutic approach for acute myeloid leukemia (AML). This study demonstrates that arming NK cells with a specific chimeric antigen receptor (CAR) significantly improves their antitumor responses to AML while avoiding off-target toxicity. These findings suggest the potential of using CAR-expressing NK cells for the treatment of AML.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Infectious Diseases
Manoj Kumar, Tarun Mathur, Tarani Kanta Barman, Tridib Chaira, Ram Kumar, Vattan Joshi, Manisha Pandya, Lalima Sharma, Kunihiko Fujii, Mahadev Bandgar, Balasaheb Jadhav, Ramesh Bambal, Dilip Upadhyay, Nobuhisa Masuda, Ashwani Kumar Verma, Pradip Kumar Bhatnagar
Summary: DS01750413, a novel FtsZ inhibitor, has shown promising in vitro and in vivo activity against MRSA, exhibiting potential antibacterial efficacy in reducing bacterial load and prolonging survival time in mice.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Erol C. Vatansever, Kai Yang, Aleksandra K. Drelich, Kaci C. Kratch, Chia-Chuan Cho, Kempaiah Rayavara Kempaiah, Jason C. Hsu, Drake M. Mellott, Shiqing Xu, Chien-Te K. Tseng, Wenshe Ray Liu
Summary: Through computational docking analysis, several FDA/EMA-approved drugs were found to inhibit the main protease of SARS-CoV-2, with three drugs showing strong antiviral activity by interfering with viral entry into host cells and inhibiting viral proteins in infected cells, especially bepridil demonstrating significant anti-SARS-CoV-2 activity in cell experiments.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Nuria Mut-Salud, Juan J. Guardia, Antonio Fernandez, Isabel Blancas, Houda Zentar, Jose M. Garrido, Enrique Alvarez-Manzaneda, Rachid Chahboun, Fernando Rodriguez-Serrano
Summary: In this study, the antitumor activity of taiwaniaquinoids, specifically compound C36, was investigated in vitro and in vivo. Results showed that C36 exhibited significant antitumor effects on MCF-7 cells by inducing apoptosis through caspase 9 activation and an increase in the Bax/Bcl-2 ratio. In vivo experiments also demonstrated the efficacy of C36 in reducing tumor growth and improving survival rates in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Jingru Shi, Chen Chen, Dejuan Wang, Ziwen Tong, Zhiqiang Wang, Yuan Liu
Summary: The study demonstrated that peptide WW307 displayed potent antibacterial activity against MDR bacteria, especially MRSA and Gram-negative pathogens carrying bla(NDM-5), mcr-1 or tet(X4). Additionally, WW307 showed great biofilm inhibition and eradication activity. Safety and stability experiments also indicated that WW307 had potential as a candidate for combating MDR pathogens.
Article
Immunology
Niura Madalena Bila, Caroline Barcelos Costa-Orlandi, Carolina Orlando Vaso, Jean Lucas Carvalho Bonatti, Leticia Ribeiro de Assis, Luis Octavio Regasini, Carla Raquel Fontana, Ana Marisa Fusco-Almeida, Maria Jose Soares Mendes-Giannini
Summary: The study evaluated the efficacy of 2-hydroxychalcone in anti-dermatophytic and anti-biofilm activity, demonstrating its inhibitory effects on early-stage and mature biofilms and enhanced efficacy under photodynamic therapy. Furthermore, 2-hydroxychalcone targets ergosterol, promotes the generation of reactive oxygen species, and induces fungal cell death by apoptosis and necrosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Plant Sciences
M. S. Nair, Y. Huang, D. A. Fidock, M. J. Towler, P. J. Weathers
Summary: The study found that A3, BUR, MED, and SAM cultivars of Artemisia annua have strong activity against five variants of SARS-CoV-2, potentially providing a cost-effective therapy to help combat the rapid global spread of these variants.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shariq M. Zaman, Marjorie A. Jones
Summary: In this study, the inhibitory effect of a specific alkylphenol natural product, anaephene B, and its synthesized derivatives on the protozoan parasite Leishmania tarentolae was tested. Interestingly, these compounds showed similar potency against Leishmania as they do against drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, all compounds tested in this study were able to completely inhibit L. tarentolae in vitro. This study enhances our understanding of the structure-activity relationship (SAR) between anaephene B and its analogues for potential pharmaceuticals against Leishmania infections.
Article
Chemistry, Medicinal
Jian-Fei Bai, Somi Reddy Majjigapu, Bernard Sordat, Sophie Poty, Pierre Vogel, Pilar Elias-Rodriguez, Antonio J. Moreno-Vargas, Ana T. Carmona, Irene Caffa, Moustafa Ghanem, Amr Khalifa, Fiammetta Monacelli, Michele Cea, Inmaculada Robina, Consuelo Gajate, Faustino Mollinedo, Axel Bellotti, Aimable Nahimana, Michel Duchosal, Alessio Nencioni
Summary: FK866, a known NAMPT inhibitor with anti-cancer activity, showed anti-proliferative activity in PDAC cell lines. By synthesizing FK866 analogues, we identified several compounds with potent cell growth inhibitory activity. The best compounds were benzamide analogues of FK866.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Reiner Noschka, Fanny Wondany, Gonul Kizilsavas, Tanja Weil, Gilbert Weidinger, Paul Walther, Jens Michaelis, Steffen Stenger
Summary: Gran1, a synthetic fragment of Granulysin, demonstrates efficient antimicrobial activity against Mycobacterium tuberculosis and clinically relevant non-tuberculous mycobacteria. It interacts with the surface of Mtb, causing lethal distortions of the cell wall, while showing no off-target effects in primary human cells or zebrafish embryos. Gran1 is selectively internalized by macrophages, restricting the proliferation of the pathogen, and its hypothesis-driven design serves as a powerful approach for identifying small bioactive compounds with specific antimicrobial activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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.
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
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
Microbiology
Sarah Vascellari, Christina Orru, Bradley Groveman, Sabiha Parveen, Giuseppe Fenu, Giada Pisano, Giuseppe G. Piga, Giulia L. Serra, Valentina Oppo, Daniela Murgia, Andrea Perra, Fabrizio A. Angius, Andrew L. Hughson, Cathryn A. Haigh, Aldo L. Manzin, Giovanni A. Cossu, Byron L. Caughey
Summary: The study demonstrates that the upper intestine of Parkinson's disease patients contains abnormal α-synuclein aggregates, which can serve as early accurate biomarkers for the disease and a cause of gut dysfunction. The research also suggests that the duodenum may be a source or a destination for pathological, self-propagating α-synuclein assemblies.
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
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.