Article
Pharmacology & Pharmacy
Michael D. Scholle, Patrick T. O'Kane, Sandra Dib, Zachary A. Gurard-Levin
Summary: This study describes a duplexed biochemical assay that can efficiently screen potential drugs against COVID-19. The results provide insights into the structural features required for inhibiting the activity of 3CLpro and guide the development of optimized antiviral compounds.
ANTIVIRAL RESEARCH
(2022)
Review
Biotechnology & Applied Microbiology
Molly K. Roe, Nathan A. Junod, Audrey R. Young, Dia C. Beachboard, Christopher C. Stobart
Summary: Coronavirus protease nsp5 (M-pro, 3CL(pro)) is a key target for coronavirus therapeutics due to its crucial role in the proteolytic processing of viral replicase polyproteins. This review discusses the structure, function, and efforts to develop inhibitors targeting nsp5, providing potential innovative strategies for effective therapeutics against the coronavirus protease.
JOURNAL OF GENERAL VIROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Lukas Wettstein, Frank Kirchhoff, Jan Muench
Summary: TMPRSS2 is a crucial protease with widespread expression in various organs, playing a role in the entry processes of different respiratory viruses. Inhibiting TMPRSS2 activity is a promising strategy for blocking viral infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Cheng Liu, Sandro Boland, Michael D. Scholle, Dorothee Bardiot, Arnaud Marchand, Patrick Chaltin, Lawrence M. Blatt, Leonid Beigelman, Julian A. Symons, Pierre Raboisson, Zachary A. Gurard-Levin, Koen Vandyck, Jerome Deval
Summary: The study evaluated SARS-CoV-2 3CLpro inhibitors using a novel enzymatic assay combining SAMDI-MS and rhinovirus HRV3C protease, showing high substrate specificity for each enzyme. The inhibitors were classified into three categories based on their potency against 3CLpro and HRV3C, guiding the design of virus-specific or broad-spectrum cysteine protease inhibitors against coronaviruses and rhinoviruses.
ANTIVIRAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Cheng Liu, Sandro Boland, Michael D. Scholle, Dorothee Bardiot, Arnaud Marchand, Patrick Chaltin, Lawrence M. Blatt, Leonid Beigelman, Julian A. Symons, Pierre Raboisson, Zachary A. Gurard-Levin, Koen Vandyck, Jerome Deval
Summary: This study evaluated the effects of different protease inhibitors on SARS-CoV-2 3CLpro and HRV3C using a novel assay, showing that different inhibitors have varying degrees of selectivity for these two enzymes.
ANTIVIRAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zhiqiang Pang, Guangyan Zhou, Jasmine Chong, Jianguo Xia
Summary: This study conducted a comprehensive meta-analysis of global metabolomics datasets from three countries to identify key metabolic signatures characterizing COVID-19 disease progression and clinical outcomes, providing important insights for clinical care and therapeutics development.
Article
Chemistry, Multidisciplinary
Jennifer Grant, Blaise R. Kimmel, Lindsey C. Szymczak, Juliet Roll, Milan Mrksich
Summary: This paper presents a method that combines a microfluidic device and self-assembled monolayers to calculate the cooperativity in binding of calcium ions to PAD2. The method uses a small amount of enzyme solution and fluidic inputs, and utilizes iSAMDI to analyze the reactions. This work establishes a high-throughput and label-free approach for studying enzyme-ligand interactions and expands the applicability of microfluidics and MALDI imaging mass spectrometry.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Ling Ma, Quanjie Li, Yongli Xie, Jianyuan Zhao, Dongrong Yi, Saisai Guo, Fei Guo, Jing Wang, Long Yang, Shan Cen
Summary: In this study, a cell-based assay for screening inhibitors against SARS-CoV-2 3CLpro was established using bioluminescence resonance energy transfer (BRET) technology. The assay was applied to screen a collection of known HIV/HCV protease inhibitors, and it was found that simeprevir showed the most potency against 3CLpro with the ability to bind to its active site pocket. This research demonstrates the feasibility of using the cell-based BRET assay for screening 3CLpro inhibitors and supports the potential of simeprevir for the development of such inhibitors.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ling Ma, Yongli Xie, Mei Zhu, Dongrong Yi, Jianyuan Zhao, Saisai Guo, Yongxin Zhang, Jing Wang, Quanjie Li, Yucheng Wang, Shan Cen
Summary: In this study, Darunavir derivatives that inhibit SARS-CoV-2 3CL(pro) were identified through a high-throughput screening method. These compounds showed favorable antiviral activity and similar potency against Omicron variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Fereshteh Noroozi Tiyoula, Hassan Aryapour
Summary: This study explored the unbinding pathways of two SARS-CoV and SARS-CoV-2 3CLpro noncovalent inhibitors from a comparative perspective. The study found common weak points for selected inhibitors that could not interact significantly with a binding pocket at specific residues.
Article
Multidisciplinary Sciences
Kodai Abe, Yasuaki Kabe, Susumu Uchiyama, Yuka W. Iwasaki, Hirotsugu Ishizu, Yoshifumi Uwamino, Toshiki Takenouchi, Shunsuke Uno, Makoto Ishii, Takahiro Maruno, Masanori Noda, Mitsuru Murata, Naoki Hasegawa, Hideyuki Saya, Yuko Kitagawa, Koichi Fukunaga, Masayuki Amagai, Haruhiko Siomi, Makoto Suematsu, Kenjiro Kosaki
Summary: Recent clinical trial showed 3CL(pro) inhibitor significantly reduces risk of hospitalization/death, while SARS-CoV-2 sub-lineage with reduced 3CL(pro) enzymatic activity exhibits milder clinical course. Structural perturbation surrounding substrate-binding region of mutant 3CL(pro) may explain the decreased activity.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Zhengnan Shen, Kiira Ratia, Laura Cooper, Deyu Kong, Hyun Lee, Youngjin Kwon, Yangfeng Li, Saad Alqarni, Fei Huang, Oleksii Dubrovskyi, Lijun Rong, Gregory R. J. Thatcher, Rui Xiong
Summary: Researchers have discovered a new antiviral drug that targets the SARS-CoV-2 papain-like protease (PLpro) to inhibit viral replication and improve antiviral potency in human cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Hai Huang, Ping-Fang Hu, Liang-Liang Sun, Yi-Bin Guo, Qiong Wang, Zhi-Min Liu, Ji-Zhong Yin, Pei-Mei Shi, Zong-Li Yuan, Wei-Fen Xie
Summary: This study suggests that high-dose ulinastatin treatment can potentially be beneficial for patients with Covid-19, helping to improve their clinical symptoms and prevent disease deterioration.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2022)
Review
Virology
Varada Anirudhan, Hyun Lee, Han Cheng, Laura Cooper, Lijun Rong
Summary: The review provides information on potential treatment strategies for COVID-19 that target the essential proteins of the virus, specifically 3CL(pro) and PLpro, which are key in inhibiting viral replication and may offer insights from previous experience with SARS-CoV.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Chemistry, Analytical
Evans C. Wralstad, Jessica Sayers, Ronald T. Raines
Summary: The main protease 3CL(pro) of SARS-CoV-2 is a dimeric enzyme that plays a crucial role in viral replication. This study used enzymatic methods to characterize the dimerization and catalytic efficiency of SARS-CoV-2 3CL(pro) and found that the enzyme forms a dimer at pH 7.5 with high catalytic activity. The enzymatic activity decreases in solutions of high ionic strength.
ANALYTICAL CHEMISTRY
(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
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.
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
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
Plant Sciences
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Johan Neyts, Christophe Pannecouque, Tom Vermeyen, Wouter A. Herrebout, Luc Pieters, Emmy Tuenter
Summary: Scadoxus multiflorus is traditionally used for respiratory problems and this study investigated its alkaloidal composition. A previously undescribed alkaloid and fourteen known ones were identified. Some of the alkaloids exhibited weak antiviral activity against SARS-CoV-2, highlighting the potential of S. multiflorus as a source for anti-SARS-CoV-2 Amaryllidaceae alkaloid scaffolds.
PHYTOCHEMISTRY LETTERS
(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)
Article
Plant Sciences
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Johan Neyts, Christophe Pannecouque, Tom Vermeyen, Wouter A. Herrebout, Luc Pieters, Emmy Tuenter
Summary: A new alkaloid, along with 17 known alkaloids, was isolated and identified from Pancratium maritimum using advanced probabilistic methods and spectroscopic techniques. Assessment of their anti-SARS-CoV-2 activity and cytotoxicity revealed several compounds with weak antiviral potency at non-toxic concentrations, while some compounds showed cytotoxicity.
PHYTOCHEMISTRY LETTERS
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Zhenzhen Shi, Xin Zhang, Niels Cremers, Johan Neyts, Harel Dahari, Suzanne Kaptein
JOURNAL OF HEPATOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Kalliopi Pervolaraki, Jean-Christophe Vanherck, Charlene Marcadet, Lieven Verhoye, Amse De Meyer, Madina Rasulova, Heyrhyoung Lyoo, Jasmine Paulissen, Hendrik Jan Thibaut, Kristof De Vos, Patrick Chaltin, Johan Neyts, Pieter Annaert, Philip Meuleman, Arnaud Marchand, Matthias Versele, Stan van de Graaf
JOURNAL OF HEPATOLOGY
(2023)