Article
Biochemistry & Molecular Biology
Francesca Curreli, Young D. Kwon, Isabella Nicolau, Giancarla Burgos, Andrea Altieri, Alexander V. Kurkin, Raffaello Verardi, Peter D. Kwong, Asim K. Debnath
Summary: As part of the effort to discover drugs targeting HIV-1 entry, this study investigates the antiviral activity and crystal structures of two novel inhibitors in complex with a gp120 core. The results show that NBD-14204 exhibits better antiviral activity and sensitivity to certain mutants, making it a promising compound for further optimization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yue Li, Pengzhen Zhong, Junna Zhao, Zexi Pan, Chen Zhang, Dongmei Cui
Summary: In this study, a selective approach for synthesizing N-([1,3,5]triazine-2-yl) a-ketoamides and N-([1,3,5]triazine-2-yl) amides from ketones with 2-amino[1,3,5]triazines through oxidation and oxidative C-C bond cleavage reaction was reported. The transformation proceeds under mild conditions, provides good functional group tolerance and chemoselectivity, and will serve as a valuable tool for the synthesis of bioactive products.
Article
Chemistry, Organic
Pengzhen Zhong, Cheng Zhang, Yue Li, Chengwu Su, Chen Zhang, Dong-Mei Cui
Summary: An efficient method for the synthesis of alpha-(1,3,5-triazinylthio)-ketones from 1,3-dicarbonyl compounds with 1,3,5-triazine-2-thiols has been developed. The reaction involves C-C bond cleavage and C-S bond reconstruction of 1,3-dicarbonyl compounds, and can tolerate beta-keto esters, beta-keto amides, and 1,3-diones. In addition, the annulation of 1,3,5-triazine-2-thiols with chalcones has been achieved for the synthesis of thiazolo-[3,2-a]-[1,3,5]-triazines in moderate to good yields, and with a broad functional group tolerance.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Wanqiu Zhao, Cheng Zhang, Pengzhen Zhong, Wei Zhou, Chen Zhang, Dong-Mei Cui
Summary: A new method for the synthesis of imidazo[1,2-a][1,3,5]triazines using an I-2-mediated annulation of 2-amino[1,3,5]triazines and ketones is presented. The reaction conditions can be changed to obtain a different class of compounds tethered with an additional 1,2-dicarbonyl motif. These new methods are practical and applicable on a gram scale.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Lijuan Liu, Zhichao Shi, Xun Zhang, Feng Zhan, Jin-Shun Lin, Yuyang Jiang
Summary: This study has developed a novel reaction method for the efficient synthesis of diverse α-amino tertiary alkylperoxides. Mechanistic investigations and useful synthetic applications of the products have also been presented.
CHEMISTRY-AN ASIAN JOURNAL
(2021)
Article
Multidisciplinary Sciences
Shouwen Du, Ruchao Peng, Wang Xu, Xiaoyun Qu, Yuhang Wang, Jiamin Wang, Letian Li, Mingyao Tian, Yudong Guan, Jigang Wang, Guoqing Wang, Hao Li, Lingcong Deng, Xiaoshuang Shi, Yidan Ma, Fengting Liu, Minhua Sun, Zhengkai Wei, Ningyi Jin, Wei Liu, Jianxun Qi, Quan Liu, Ming Liao, Chang Li
Summary: This study presents the cryo-EM structure of SFTSV virion and discusses the mechanisms of viral assembly, membrane fusion, and antibody neutralization.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
You Zhang, Juan Carlos de la Torre, Gregory B. Melikyan
Summary: This study investigates the role of human LAMP1 in LASV fusion and reveals that ectopic expression of hLAMP1 accelerates the kinetics of small fusion pore formation but only modestly increases LASV fusion and infection. Furthermore, it is found that hLAMP1 is involved in the dilation of LASV fusion pores in the late stage of fusion. These findings shed light on the previously unappreciated role of hLAMP1 in promoting dilation of LASV fusion pores.
Article
Immunology
Leslie S. Wolfe, James G. Smedley III, Niket Bubna, Althaf Hussain, Richard Harper, Sigma Mostafa
Summary: The preclinical development of vaccine candidates is crucial for the discovery and manufacture of vaccines for human clinical trials. In this study, an exploratory clinical approach was used to develop multiple gp120 envelope proteins as vaccine antigens, resulting in the successful production of four gp120 envelope protein variants using a harmonized platform development strategy.
Review
Virology
Tianshu Xiao, Yongfei Cai, Bing Chen
Summary: HIV-1 infection begins with virion attachment to host cell membrane through Env, binding to receptors CD4 and coreceptors CCR5/CXCR4; understanding the structural biology of HIV-1 Env aids in designing antiviral therapeutics targeting viral entry.
Article
Biochemistry & Molecular Biology
Nabeelah Bibi Sadeer, Juliano G. Haddad, Mohammed Oday Ezzat, Philippe Despres, Hassan H. Abdallah, Gokhan Zengin, Ibtesam Mohammad Alshamrani, Jameel Barnawi, Asaad Khalid, Ashraf N. Abdalla, Bao Le Van, Chaker El Kalamouni, Mohamad Fawzi Mahomoodally
Summary: The recent appearance of Zika virus in Brazil is a global public health threat and should be taken seriously by international authorities. In this study, it was found that the mangrove plant Rhizophora mucronata collected in Mauritius has anti-ZIKV activity. The fruit and root extracts of R. mucronata were effective inhibitors of ZIKV infection in human epithelial cells.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Immunology
Patrick O. Byrne, Jason S. McLellan
Summary: Structure-based vaccine design aims to stabilize antigens in a vulnerable conformation by exploiting knowledge of their architecture. This article summarizes the general principles of structure-based vaccine design and discusses the major types of sequence modifications. It also reviews the recent applications of these principles in vaccine-design efforts for several viral families.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Woohyung Jeon, Ramil Baiazitov, Matteo Chierchia, Kyle Niederer, Hongyu Ren, Young-Choon Moon, Bradley B. Gilbert
Summary: This article reports a simple synthetic method for preparing various di- and trifluoromethyl-s-triazines from readily available starting materials. Trichloromethyl-substituted triazine electrophiles were obtained in good yield and reacted with amine nucleophiles to afford aminotriazine products in good to excellent yield. The nucleophilic aromatic substitution reaction showed broad scope, smoothly proceeding with both aromatic and aliphatic amines in the presence of non-participating functional groups, and requiring only a catalytic amount of 4-DMAP without stoichiometric base.
HELVETICA CHIMICA ACTA
(2023)
Article
Virology
Sachith Polpitiya Arachchige, Wyatt Henke, Maria Kalamvoki, Edward B. Stephens
Summary: The study demonstrates that the gD glycoprotein of HSV-1 restricts HIV-1 infectivity, with its cytoplasmic tail domain playing a significant role in restriction activity, while the transmembrane domain of gB influences its incorporation into HIV-1 particles. Swapping domains between gD and gB shed light on the importance of gD cell surface expression and its interaction with HIV-1 particles.
JOURNAL OF VIROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nastasja Palombi, Annalaura Brai, Martina Gerace, Salvatore Di Maria, Francesco Orofino, Federico Corelli
Summary: Enveloped viruses are a class of pathogens responsible for serious diseases, with their outer membrane making them more resistant to enzymes and less susceptible to host immune defenses. Developing effective approaches to combat enveloped virus infections is a major challenge in antiviral therapy. Targeting the envelope of enveloped viruses with broad-spectrum antiviral compounds is of great interest when specific drugs or vaccines are not available to block viral infections.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Valerie Lorin, Ignacio Fernandez, Guillemette Masse-Ranson, Melanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gerard Pehau-Arnaudet, Dominik Hrebik, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, Francois Bontems, James P. Di Santo, Felix A. Rey, Hugo Mouquet
Summary: Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies is crucial for vaccine design. This study found that multiple B cell lineages in HIV-1 viremic controllers can develop antibodies targeting a unique site of vulnerability on the virus, primarily composed of specific sugar residues. These antibodies exhibit high neutralizing capacity and delay viral rebound in animal models.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Iwona E. Glowacka, Katarzyna Gawron, Dorota G. Piotrowska, Mirthe Graus, Graciela Andrei, Dominique Schols, Robert Snoeck, Anita Camps, Emiel Vanhulle, Kurt Vermeire
Summary: In this study, a series of 48 hybrids were synthesised and evaluated for antiviral activity. The hybrids contained a diethoxyphosphoryl group connected to the triazole moiety via ethylene or propylene linker, and substituted benzyl or benzoyl function in the quinazoline-2,4-dione moiety. The hybrids showed potent antiviral activities against Respiratory Syncytial Virus (RSV), with some weak activity against varicella zoster virus and human cytomegalovirus.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Shenghua Gao, Letian Song, Hongtao Xu, Antonios Fikatas, Merel Oeyen, Steven De Jonghe, Fabao Zhao, Lanlan Jing, Dirk Jochmans, Laura Vangeel, Yusen Cheng, Dongwei Kang, Johan Neyts, Piet Herdewijn, Dominique Schols, Peng Zhan, Xinyong Liu
Summary: DF-47 and DF-51 were identified as effective inhibitors of SARS-CoV-2/DENV polymerase through RdRp inhibition screening and in vitro antiviral study. In silico simulation revealed stable binding modes between DF-47/DF-51 and SARS-CoV-2/DENV RdRp, including chelating with Mg2+ near the polymerase active site. These polyphenols have the potential to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with a new scaffold.
Article
Chemistry, Medicinal
Max Van Hoof, Sandra Claes, Matic Proj, Tom Van Loy, Dominique Schols, Stanislav Gobec, Wim Dehaen, Steven De Jonghe
Summary: CCR7 signaling is important in immune cell and cancer cell migration, chronic inflammatory disorders, and lymph node metastases. However, there is currently a lack of potent and selective small molecule CCR7 antagonists. In this study, a triazolo[4,5-d]pyrimidine analogue was discovered as a potential CCR7 antagonist through screening. Structural optimization of this analogue resulted in improved potency and selectivity, with one derivative showing the most promising activity against CCR7 and CXCR2. Molecular docking studies confirmed the binding mode of these derivatives in CCR7 and CXCR2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Max Van Hoof, Sandra Claes, Katrijn Boon, Tom Van Loy, Dominique Schols, Wim Dehaen, Steven De Jonghe
Summary: Upregulated CXCR2 signalling is common in inflammatory, autoimmune, neurodegenerative diseases, and cancer, making CXCR2 antagonism a promising therapeutic strategy. Previous research identified a pyrido[3,4-d]pyrimidine analogue as a potent CXCR2 antagonist. This study aims to improve the CXCR2 antagonistic potency through structural modifications, but most new analogues lacked CXCR2 antagonism except for a 6-furanyl-pyrido[3,4-d]pyrimidine analogue.
Article
Plant Sciences
Katarina Magdalenic, Ulrike Ronse, Steven De Jonghe, Leentje Persoons, Dominique Schols, Julie De Munck, Charlotte Grootaert, John Van Camp, Matthias D'hooghe
Summary: Curcumin, a natural product, has broad biological activities, including anticancer properties. However, it is poorly absorbed by the body and shows non-specific activity in biological assays. Recent research has led to the development of benzothiazepane-based molecules with promising biological and drug-like properties. In this study, 14 new compounds were synthesized and tested for their cytotoxicity against cancer cells, providing insights into the structure-activity relationships of this new class of compounds.
PHYTOCHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Merel Oeyen, Eef Meyen, Dominique Schols
Summary: Cell-based electrical impedance technology can be used to monitor the consequences of Zika virus infection and cell replication in real time without the use of labels or invasive methods, providing real-time data. This method can also be used for the evaluation and characterization of antiviral compounds.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Chemistry, Medicinal
Xiao Jia, Dominique Schols, Chris Meier
Summary: We synthesized and evaluated three different nucleotide prodrug systems. These prodrugs showed remarkable antiviral activity against HIV in infected cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Papisetti Venkatesham, Dominique Schols, Leentje Persoons, Sandra Claes, Akanksha Ashok Sangolkar, Raju Chedupaka, Rajeswar Rao Vedula
Summary: A series of 1,2,4-triazolothiazoles were efficiently synthesized using a one-pot process in the presence of EtOH/DMF. The synthesized compounds showed high purity and confirmed structures through spectral analysis. Among them, two derivatives displayed inhibitory activity against both HIV-1 and HIV-2, while seven compounds showed selectivity towards HIV-2. Compound 5f exhibited promising activity against Zika virus. Molecular docking studies were also conducted for the most active compounds.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Organic
Jose-Maria Orduna, Natalia del Rio, Maria-Jesus Perez-Perez
Summary: Reductive amination of functionalized aldehydes with aniline derivatives of adenine and closely related 7-deazapurines was successfully performed using H-cube technology, avoiding the drawbacks of traditional batch protocols. This method allows for high conversion and easy work-up by evaporation, without the need for acids, making it compatible with acid-sensitive protecting groups.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
J. Kaes, E. Vanhulle, L. Seldeslachts, C. Hooft, H. Beeckmans, X. Jin, P. Kerckhof, J. Van Slambrouck, D. Van Raemelonck, G. Vande Velde, L. Naesens, D. Schols, L. J. Ceulemans, R. Vos, K. Vertneire, B. M. Vanaudenaerde
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Chemistry, Multidisciplinary
Valeriya S. S. Bolshakova, Olga A. A. Kraevaya, Alexander S. S. Peregudov, Vitaliy Yu. Markov, Svetlana V. V. Kostyuk, Dominique Schols, Alexander F. F. Shestakov, Pavel A. A. Troshin
Summary: We report a new reaction between thiophene derivatives and fullerene derivatives, resulting in a family of C-60 fullerene compounds with three different types of functional aromatic addends attached to the carbon cage. The discovered reaction provides a pathway for the synthesis of novel C-60 fullerene derivatives with promising antioxidant and antiviral properties.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Maria Karelou, Dionysis Kampasis, Amalia D. Kalampaliki, Leentje Persoons, Andreas Kraemer, Dominique Schols, Stefan Knapp, Steven De Jonghe, Ioannis K. Kostakis, Sotiris S. Nikolaropoulos
Summary: Sixteen new 2-substituted quinazolines were synthesized and evaluated for their anti-proliferative activity against multiple cancer cell lines. Compound 17 showed remarkable activity against the majority of tested cell lines.
Article
Chemistry, Multidisciplinary
Jin-Bu Xu, Peng Wen, Neng Wang, Xiaohuan Li, Jia-Hong Li, Steven De Jonghe, Dominique Schols, Feng-Zheng Chen, Feng Gao
Summary: The rare Euphorbia glucoside E (1) was efficiently synthesized from the abundant lathyrane-type Euphorbia factor L(1) using a visible-light-induced tandem reaction with Sc(OTf)3 catalyst. Eupholathones 2 and 3 were also obtained by changing the reaction solvent. This method provides a convenient approach for constructing the scarce Euphorbia glucosides from lathyrane-type Euphorbia diterpenes and confirms their biogenetic relationship from a chemical perspective. Notably, compound 1 exhibited significant anti-HIV activity.
CHEMICAL COMMUNICATIONS
(2023)