Editorial Material
Multidisciplinary Sciences
Scott B. Biering, Eva Harris
Summary: The compound JNJ-A07 shows promising activity against the dengue virus in mouse models, offering hope for a treatment for this prevalent mosquito-borne viral disease in humans.
Review
Immunology
Harun Norshidah, Chiuan Herng Leow, Kamarulzaman Ezatul Ezleen, Habibah A. Wahab, Ramachandran Vignesh, Azhar Rasul, Ngit Shin Lai
Summary: The increase in viral infectious diseases is a global concern. Researchers have conducted numerous studies on viral epidemiology, structure and function, treatment targets, vaccines, and drugs. The development of the Dengvaxia vaccine has been a milestone in dengue treatment, but vaccines have limitations. Therefore, researchers are developing dengue antivirals. This review discusses strategies for finding novel dengue NS2B/NS3 protease inhibitors through in silico and in vitro approaches, aiming to encourage further developments in this area.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Joshua A. Jackman, Bo Kyeong Yoon, Lei Ouyang, Nan Wang, Abdul Rahim Ferhan, Jaeyun Kim, Tetsuro Majima, Nam-Joon Cho
Summary: This article discusses the importance of developing nanomaterials for the treatment and prevention of viral infections, as well as the latest advances in biomimetic nanomaterials in this field, mainly covering nanomaterial-enhanced viral replication inhibitors, biomimetic virus particle capture schemes, and nanoparticle vaccines.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Thippayawan Ratanakomol, Sittiruk Roytrakul, Nitwara Wikan, Duncan R. Smith
Summary: Berberine has virucidal activity against dengue, Zika, and chikungunya viruses, potentially through AMPK activation and disruption of lipid metabolism.
Review
Pharmacology & Pharmacy
Paul T. Winnard, Farhad Vesuna, Venu Raman
Summary: DDX3X, a multifunctional protein utilized by various viruses, plays a crucial role in viral metabolism. Modulating the functions of DDX3 during viral infections could effectively suppress viral production and have a significant impact on safely and efficiently subduing a broad spectrum of viral infections.
ANTIVIRAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Sangwoo Nam, Hyo Gyeong Na, Eun Hye Oh, Eunhye Jung, Yeon Hee Lee, Eun Ju Jeong, Yu-Da Ou, Bin Zhou, Sunjoo Ahn, Jin Soo Shin, Soo Bong Han, Yun Young Go
Summary: A series of 1,2,4-oxadiazole derivatives with antiviral activity against Zika virus (ZIKV) infection were identified and 28 new compounds were designed, synthesized, and evaluated. Among these compounds, 4-(5-phenyl-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-ylmethyl)aniline showed potent antiviral activity against ZIKV infections and also exhibited activity against other viruses of the Flaviviridae family.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Article
Virology
Kristie A. Yamamoto, Kevin Blackburn, Michael B. Goshe, Dennis T. Brown, Edimilson Migoswski, Isabele B. Campanhon, Monica F. Moreira, Davis F. Ferreira, Marcia R. Soares
Summary: In this study, the antiviral activity of tizoxanide (TIZ) against dengue virus type 2 (DENV-2) was evaluated. TIZ showed inhibitory effects on DENV-2 replication mainly after virus penetration and before complete replication of the viral genome. It also interfered with cellular processes and activated immune response genes, leading to a decrease in DENV-2 production. TIZ holds promise as a therapeutic molecule for DENV-2 infections.
Article
Virology
Bowen Yi, Benjamin Xuan Zheng Chew, Huixin Chen, Regina Ching Hua Lee, Yuhui Deborah Fong, Wei Xin Chin, Chee Keng Mok, Justin Jang Hann Chu
Summary: Catechin, a natural polyphenol compound, has been evaluated as a potential inhibitor of dengue virus (DENV) infection. It was shown to inhibit a specific stage of the DENV replication cycle and affect viral protein translation. Catechin demonstrated inhibitory effects on all four DENV serotypes and chikungunya virus (CHIKV), suggesting its potential as a starting scaffold for the development of antivirals against DENV infection.
Review
Virology
Victor Cardoso-Jaime, Chinmay Vijay Tikhe, Shengzhang Dong, George Dimopoulos
Summary: Insect hemocytes play a critical role in immune responses, but our understanding of their antiviral potential is limited. They express humoral factors and immune pathways that restrict viral infections. However, the specific mechanisms behind their regulation of viral infections are still unclear.
Review
Pharmacology & Pharmacy
Thennakoon M. Sampath U. Gunathilake, Yern Chee Ching, Hiroshi Uyama, Cheng Hock Chuah
Summary: Viral diseases, particularly coronaviruses like SARS-CoV, MERS-CoV, and SARS-CoV-2, pose a serious threat to human health and have become a global public health crisis, with COVID-19 caused by SARS-CoV-2 being a severe pandemic. Nanomaterials offer a technology platform that can address key issues in viral infection treatment and have the potential to play a crucial role in vaccine and therapeutic development.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2021)
Article
Immunology
Ting-Jing Shen, Vu Thi Hanh, Thai Quoc Nguyen, Ming-Kai Jhan, Min-Ru Ho, Chiou-Feng Lin
Summary: Research has shown that the antiemetic drug metoclopramide (MCP) targeting D2R can effectively inhibit dengue virus infection and reduce viral replication, making it a potential new strategy for treating dengue virus.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shih-Che Weng, Yu-Xian Zhou, Shin-Hong Shiao
Summary: This study developed a novel antiviral approach using a virus-inducible gene expression system to block the replication and transmission of dengue virus and Zika virus. The system successfully inhibited viral replication and production of infectious virus particles both in vitro and in mosquitoes.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Aditya R. Kolli, Florian Calvino-Martin, Julia Hoeng
Summary: This study predicts the cellular and lysosomal concentrations of chloroquine and hydroxychloroquine in vivo using an in vitro ion-trapping kinetic model and a physiologically based pharmacokinetic model. The results show that the effective concentrations observed in vitro cannot be achieved with oral administration, but aerosolized administration can reach high concentrations in the respiratory tract. Achieving effective cytosolic concentrations and adequate lysosomal levels is crucial for treating viral respiratory infections.
PHARMACEUTICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Hrithika Panday, Saurabh Kumar Jha, Mohammed Al-Shehri, Siva Prasad Panda, Rashmi Rana, Nada F. Alwathinani, Esam I. Azhar, Vivek Dhar Dwivedi, Abhimanyu Kumar Jha
Summary: RNA-dependent RNA polymerase (RdRp) is an important drug target for inhibiting dengue virus (DENV) and has received attention in antiviral drug discovery. In this study, we screened 121 natural compounds from Litsea cubeba against DENV RdRp using computer-based drug discovery approaches. We identified four potential compounds (Ushinsunine, Cassameridine, (+)-Epiexcelsin, (-)-Phanostenine) with good binding scores and stable interactions with the target protein. Molecular dynamics simulation studies and post-simulation analysis were performed to assess the stability of the complexes and the drugs' interaction with the target protein. The findings suggest that phytochemicals derived from Litsea cubeba could be a therapeutic solution for controlling DENV infection.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Maria Mora Gonzalez Lopez Ledesma, Guadalupe Costa Navarro, Horacio M. Pallares, Ana Paletta, Federico De Maio, Nestor G. Iglesias, Leopoldo Gebhard, Santiago Oviedo Rouco, Diego S. Ojeda, Luana de Borba, Maria Giraldo, Ricardo Rajsbaum, Ana Ceballos, Nevan J. Krogan, Priya S. Shah, Andrea Gamarnik
Summary: This study identifies a viral mechanism in which the DENV protein NS5 degrades the host protein ERC1 to limit NF-KB activation and cytokine secretion, reducing cell migration. The findings suggest the potential application of this mechanism in designing dengue vaccines.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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.
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.
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
Multidisciplinary Sciences
Olivia Goethals, Suzanne J. F. Kaptein, Bart Kesteleyn, Jean-Francois Bonfanti, Liesbeth Van Wesenbeeck, Dorothee Bardiot, Ernst J. Verschoor, Babs E. Verstrepen, Zahra Fagrouch, J. Robert Putnak, Dominik Kiemel, Oliver Ackaert, Roel Straetemans, Sophie Lachau-Durand, Peggy Geluykens, Marjolein Crabbe, Kim Thys, Bart Stoops, Oliver Lenz, Lotke Tambuyzer, Sandra De Meyer, Kai Dallmeier, Michael K. McCracken, Gregory D. Gromowski, Wiriya Rutvisuttinunt, Richard G. Jarman, Nicos Karasavvas, Franck Touret, Gilles Querat, Xavier de Lamballerie, Laurent Chatel-Chaix, Gregg N. Milligan, David W. C. Beasley, Nigel Bourne, Alan D. T. Barrett, Arnaud Marchand, Tim H. M. Jonckers, Pierre Raboisson, Kenny Simmen, Patrick Chaltin, Ralf Bartenschlager, Willy M. Bogers, Johan Neyts, Marnix Van Loock
Summary: Dengue is a major health threat with millions of infections and thousands of deaths each year. Currently, there are no antiviral drugs available for the treatment or prevention of dengue. However, researchers have recently identified a potential target for the development of DENV inhibitors. They have developed a highly potent DENV inhibitor called JNJ-1802, which has shown promising results in inhibiting viral replication and has completed phase I clinical trials. These findings support the further development of JNJ-1802 as a first-in-class antiviral agent for the prevention and treatment of dengue.
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
Sheli R. Radoshitzky, Patrick Iversen, Xianghan Lu, Jing Zou, Suzanne J. F. Kaptein, Kelly S. Stuthman, Sean A. Van Tongeren, Jesse Steffens, Ruoyu Gong, Hoa Truong, Annapurna A. Sapre, Huiling Yang, Xiaodong Xie, Jia Jun Chia, Zhijuan J. Song, Stacey M. Leventhal, Josolyn Chan, Alex Shornikov, Xin Zhang, David Cowfer, Helen Yu, Travis Warren, Tomas Cihlar, Danielle P. Porter, Johan Neyts, Pei-Yong Shi, Jay Wells, John P. Bilello, Joy Y. Feng
Summary: Remdesivir is an antiviral drug that can inhibit the infection of multiple RNA viruses, including dengue, yellow fever, Zika viruses, and Ebola virus. However, it is not effective against influenza viruses and hepatitis B, C, and E viruses.
SCIENTIFIC REPORTS
(2023)
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
Article
Infectious Diseases
Helen J. Box, Joanne Sharp, Shaun H. Pennington, Edyta Kijak, Lee Tatham, Claire H. Caygill, Rose C. Lopeman, Laura N. Jeffreys, Joanne Herriott, Megan Neary, Anthony Valentijn, Henry Pertinez, Paul Curley, Usman Arshad, Rajith K. R. Rajoli, Dirk Jochmans, Laura Vangeel, Johan Neyts, Eric Chatelain, Fanny Escudie, Ivan Scandale, Steve Rannard, James P. Stewart, Giancarlo A. Biagini, Andrew Owen
Summary: This study aimed to investigate the antiviral activity of probenecid against SARS-CoV-2, but no significant antiviral effects were observed in cell assays and animal models.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
