Article
Biochemistry & Molecular Biology
Saisai Guo, Xiaobo Lei, Yan Chang, Jianyuan Zhao, Jing Wang, Xiaojing Dong, Qian Liu, Zixiong Zhang, Lidan Wang, Dongrong Yi, Ling Ma, Quanjie Li, Yongxin Zhang, Jiwei Ding, Chen Liang, Xiaoyu Li, Fei Guo, Jianwei Wang, Shan Cen
Summary: Research has identified CDK2 as a key host factor in SARS-CoV-2 RNA replication, facilitating viral RNA synthesis, and CDK2 inhibitors have shown potential in impairing viral replication and infection.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Chemistry, Multidisciplinary
Hesong Han, Albert Vallejo Gracia, Joachim J. Roise, Lydia Boike, Kristoffer Leon, Ursula Schulze-Gahmen, Michael R. Stentzel, Teena Bajaj, Dake Chen, I. -Che Li, Maomao He, Kamyar Behrouzi, Zahra Khodabakhshi, Daniel K. Nomura, Mohammad R. K. Mofrad, G. Renuka Kumar, Melanie Ott, Niren Murthy
Summary: In this study, a-chloro amide fragment compound 1 was found to inhibit SARS-CoV-2 replication and have low reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro and has an IC50 of 18 μM for PLpro inhibition. Additionally, compound 1 exhibits low toxicity in cells and mice, with a molecular weight of 247 daltons, making it a promising lead fragment for PLpro drug discovery campaigns.
Article
Microbiology
Chao Ma, Yuhan Li, Yanan Zong, Tony Velkov, Chenxi Wang, Xinyu Yang, Ming Zhang, Zhimin Jiang, Haoran Sun, Qi Tong, Honglei Sun, Juan Pu, Munir Iqbal, Jinhua Liu, Chongshan Dai, Yipeng Sun
Summary: The influenza A virus (IAV) can activate p21 through a p53-independent pathway. p21 directly binds to the viral polymerase acidic protein, limiting IAV polymerase activity by disrupting the formation of the ribonucleoprotein complex. p21 activation promotes IRF3 activation by blocking the degradation of HO-1, leading to the activation of the type I interferon pathway.
Article
Pharmacology & Pharmacy
Quanjie Li, Dongrong Yi, Xiaobo Lei, Jianyuan Zhao, Yongxin Zhang, Xiangling Cui, Xia Xiao, Tao Jiao, Xiaojing Dong, Xuesen Zhao, Hui Zeng, Chen Liang, Lili Ren, Fei Guo, Xiaoyu Li, Jianwei Wang, Shan Cen
Summary: Corilagin has been identified as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, effectively inhibiting polymerase activity and showing potential therapeutic effects against SARS-CoV-2 infection. Combining corilagin with remdesivir also enhances the efficacy against SARS-CoV-2 RdRp.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Cell Biology
Madison S. Strine, Mia Madel Alfajaro, Vincent R. Graziano, Jaewon Song, Leon L. Hsieh, Ryan Hill, Jun Guo, Kelli L. VanDussen, Robert C. Orchard, Megan T. Baldridge, Sanghyun Lee, Craig B. Wilen
Summary: Murine norovirus (MNoV) is a model for studying human norovirus and its mechanisms of infection. This study demonstrates that diverse strains of MNoV require tuft cells for chronic enteric infection. Additionally, interferon-lambda acts directly on tuft cells to cure chronic MNoVCR6 infection, and type I and III interferons signal together via STAT1 in tuft cells to restrict MNoVCW3 tropism.
Article
Multidisciplinary Sciences
Sebastian Zeltzer, Pierce Longmire, Marek Svoboda, Giovanni Bosco, Felicia Goodrum
Summary: Human cells have multiple specialized DNA polymerases for chromosomal DNA synthesis and repair, while complex DNA viruses may rely on host polymerases for synthesis. This study shows that error-prone Y-family polymerases can restrict human cytomegalovirus genome synthesis, while other TLS polymerases are required for optimal replication. Host polymerases also suppress viral genome rearrangements, indicating their role in ensuring viral genome stability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Yingying Ma, Yanyan Han, Yuan Li, Wenlu Fan, Xin Yao, Xinning Huang, Mei Wang, Sheng Jiang, Jinghua Zhao, Xinyuan Qiao, Houhui Song, Yigang Xu
Summary: Bovine viral diarrhea virus (BVDV), an important pathogen of cattle, causes extensive economic losses in the cattle industry worldwide. The molecular interactions between BVDV and its host are complex. In this study, researchers explored the role of DHCR24-mediated cholesterol synthesis in regulating BVDV replication. They found that increased DHCR24 induced by BVDV infection promotes cholesterol production and plays a significant role in viral replication.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ahrim Lee, Jieun Sung, Dipesh S. Harmalkar, Hyeseul Kang, Hwayoung Lee, Kyeong Lee, Choongho Lee
Summary: This study aimed to elucidate the molecular mechanism of the NV replication inhibitor AC-1858, confirming its inhibitory effects on NV RNA replication. The induction of the host factor HSF-1 and its impact on NV RNA replication were also investigated, suggesting a restrictive role of HSF-1 in overall viral RNA genome replication during the NV life cycle.
BIOMOLECULES & THERAPEUTICS
(2022)
Article
Agriculture, Dairy & Animal Science
Qi Shao, Feiyu Fu, Pei Zhu, Xiangyu Yu, Jie Wang, Zhaofei Wang, Jingjiao Ma, Hengan Wang, Yaxian Yan, Yuqiang Cheng, Jianhe Sun
Summary: The pigeon MDA5 gene was cloned and studied, and it was found that MDA5 plays an important role in innate immunity by activating the interferon signal pathway to inhibit viral replication in pigeons.
Article
Microbiology
Jennifer Gribble, Laura J. Stevens, Maria L. Agostini, Jordan Anderson-Daniels, James D. Chappell, Xiaotao Lu, Andrea J. Pruijssers, Andrew L. Routh, Mark R. Denison
Summary: Recombination is essential for coronavirus diversity and the emergence of new strains. The mechanisms of CoV recombination are not well understood, but studies have shown extensive and diverse recombination products in CoVs during replication. The nsp14-ExoN protein is crucial for native recombination in CoVs, highlighting its potential as a target for inhibitors to control SARS-CoV-2 and future emerging zoonotic CoVs.
Article
Virology
Clara Pohl, Grit Szczepankiewicz, Uwe Gerd Liebert
Summary: Human noroviruses (hNoVs) are a significant cause of acute gastroenteritis worldwide. However, the lack of a reproducible in vitro cell culture system has hindered research and the development of preventive measures, therapeutic drugs, and vaccines. This study aimed to identify and optimize a suitable cell line for in vitro cultivation of hNoV. The Caco-2 cell line, which originates from the colon and spontaneously differentiates into intestinal enterocyte-like cells, was selected as a model. The results showed that differentiated cells were more susceptible to hNoV infection and produced a higher virus yield.
ARCHIVES OF VIROLOGY
(2022)
Review
Virology
Kavitha Ramaswamy, Mariya Rashid, Selvarajan Ramasamy, Tamilselvan Jayavelu, Sangita Venkataraman
Summary: This review explores the structural differences of RdRPs in RNA binding and polymerization mechanisms, based on recent studies of RdRP complexes with various cofactors, RNA moieties, analogs, and inhibitors.
Article
Biochemistry & Molecular Biology
Akash Kumar, Preeti Hooda, Anindita Puri, Radhika Khatter, Mohammed S. Al-Dosari, Neha Sinha, Mohammad K. Parvez, Deepak Sehgal
Summary: Hepatitis E Virus (HEV) is a RNA virus that requires modulation of specific enzymes for infection prevention. Methotrexate and compound A have been found to inhibit the activity of HEV helicase, thereby inhibiting HEV RNA replication.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Monica Bubenik, Pavel Mader, Philippe Mochirian, Frederic Vallee, Jillian Clark, Jean-Francois Truchon, Alexander L. Perryman, Victor Pau, Igor Kurinov, Karl E. Zahn, Marie-Eve Leclaire, Robert Papp, Marie-Claude Mathieu, Martine Hamel, Nicole M. Duffy, Claude Godbout, Matias Casas-Selves, Jean-Pierre Falgueyret, Prasamit S. Baruah, Olivier Nicolas, Rino Stocco, Hugo Poirier, Giovanni Martino, Alexanne Bonneau Fortin, Anne Roulston, Amandine Chefson, Stephane Dorich, Miguel St-Onge, Purvish Patel, Charles Pellerin, Stephane Ciblat, Thomas Pinter, Francis Barabe, Majida El Bakkouri, Paranjay Parikh, Christian Gervais, Agnel Sfeir, Yael Mamane, Stephen J. Morris, W. Cameron Black, Frank Sicheri, Michel Gallant
Summary: This study describes the search for a selective inhibitor of DNA polymerase theta and the successful identification of RP-6685 as a potent, selective, and orally bioavailable inhibitor with potential efficacy in breast and ovarian cancer treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Weixiao Zhang, Haiyan Shen, Menglu Wang, Xuelei Fan, Songqi Wang, Nile Wuri, Bin Zhang, Haiyan He, Chunhong Zhang, Zhicheng Liu, Ming Liao, Jianfeng Zhang, Yugu Li, Jianmin Zhang
Summary: The porcine epidemic diarrhea virus (PEDV) is a highly contagious enteropathogenic coronavirus that poses a serious threat to animal and human health. This study found that fangchinoline (Fan) can inhibit PEDV infection by blocking the autophagic flux in cells. These findings will contribute to the development of new strategies for the prevention and treatment of PEDV infection.
FRONTIERS IN MICROBIOLOGY
(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
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)
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
Microbiology
Dirk Jochmans, Cheng Liu, Kim Donckers, Antitsa Stoycheva, Sandro Boland, Sarah K. Stevens, Chloe De Vita, Bert Vanmechelen, Piet Maes, Bettina Trueb, Nadine Ebert, Volker Thiel, Steven De Jonghe, Laura Vangeel, Dorothee Bardiot, Andreas Jekle, Lawrence M. Blatt, Leonid Beigelman, Julian A. Symons, Pierre Raboisson, Patrick Chaltin, Arnaud Marchand, Johan Neyts, Jerome Deval, Koen Vandyck
Summary: Paxlovid is the first oral antiviral approved for the treatment of SARS-CoV-2 infection. Research has identified mutations in the 3CLpro protease that may lead to resistance against Paxlovid. These findings are important for guiding the use of novel antiviral drugs.
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
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.
Review
Microbiology
Sergio Santos-Silva, Pedro Lopez-Lopez, Helena M. R. Goncalves, Antonio Rivero-Juarez, Wim H. M. Van der Poel, Maria Sao Jose Nascimento, Joao R. Mesquita
Summary: Swine are recognized as the main reservoir of zoonotic HEV, but data suggests that farmed ruminants may also contribute to HEV transmission. This study aimed to analyze the current research on HEV detection in farmed ruminants. The results showed an overall prevalence of HEV in farmed ruminants of 0.02%, with HEV-3 and HEV-4 being the most common genotypes. Further research is needed to understand the zoonotic potential of HEV in these animals and their products.
Article
Virology
Sofia Almeida, Paula Gouveia, Arminda Jorge, Ana Fortuna, Sandro Binda, Maria Barbi, Maria Sao Jose Nascimento, Paulo Paixao
Summary: This study summarizes the results of a 15-year observational study in which dried blood spots (DBS) were used for late diagnosis of congenital cytomegalovirus (CMV) infection. The study found that testing DBS in symptomatic children and children born to mothers with serologic diagnosis of maternal primary CMV infection can yield higher virus detection rates.
JOURNAL OF CLINICAL VIROLOGY
(2023)
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)
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)