Article
Chemistry, Medicinal
Petra Brehova, Ema Chaloupecka, Michal Cesnek, Jan Skacel, Martin Dracinsky, Eva Tloustova, Helena Mertlikova-Kaiserova, Monica P. Soto-Velasquez, Val J. Watts, Zlatko Janeba
Summary: A series of novel acyclic nucleoside phosphonates (ANPs) were synthesized and evaluated as potential adenylate cyclase inhibitors, showing promising inhibitory effects on various toxins and enzymes. Some compounds were identified as potential leads for the treatment of human inflammatory and neuropathic pain.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Karolina Vankova, Eva Dolezelova, Eva Tloustova, Dana Hockova, Alena Zikova, Zlatko Janeba
Summary: A series of novel 7-aryl-7-deazaadenine-based N-branched acyclic nucleoside phosphonates (aza-ANPs) were synthesized using the optimized Suzuki cross-coupling reaction. Compound 14h, which contains two phosphonate moieties, showed potent anti-trypanosomal activity and low micromolar cytotoxicity against leukemia and/or cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Pavel Kraina, Michal Cesnek, Eva Tloustova, Helena Mertlikova-Kaiserova, Camryn J. Fulton, Emily K. Davidson, Brenton P. Smith, Val J. Watts, Zlatko Janeba
Summary: A series of novel 7-substituted 7-deazaadefovir analogues were synthesized, and 12 of them were found to be single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin. Compound 14 was identified as a potent, non-toxic, and selective mAC2 inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Virology
Jessica Oswald, Mathew Constantine, Adedolapo Adegbuyi, Esosa Omorogbe, Anna J. Dellomo, Elana S. Ehrlich
Summary: In order to infect and replicate, viruses need to control cellular machinery and counteract antiviral proteins and restriction factors. They achieve this by regulating cellular gene expression and post-transcriptional and post-translational control. Many viruses manipulate and counteract cellular processes through modulation of post-translational modification machinery and utilizing or taking over kinases, SUMO ligases, deubiquitinases, and ubiquitin ligases. This review focuses on the interactions between three oncoviruses, Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), and human immunodeficiency virus (HIV), and the ubiquitin-proteasome system via viral-encoded or cellular E3 ubiquitin ligase activity.
Article
Virology
Ting Shi, Linlin Huang, Zhengrong Chen, Jianmei Tian
Summary: This study investigated the characteristics of primary EBV infection and reactivation in children in Suzhou, China, finding that primary EBV infection was more common in children aged 36 to <72 months and often led to infectious mononucleosis. Reactivation of EBV mainly occurred in children aged 8 to <36 months and was identified as a risk factor for hemophagocytic lymphohistiocytosis (HLH). Among reactivated patients, HLH had a higher viral load compared to EBV infection and respiratory infection.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Chemistry, Medicinal
Michal Cesnek, Michal Safranek, Martin Dracinsky, Eva Tloust'ova, Helena Mertlikova-Kaiserova, Michael P. Hayes, Val J. Watts, Zlatko Janeba
Summary: A series of potent acyclic nucleoside phosphonates (ANPs) were designed as inhibitors of bacterial ACs, showing substantial selectivity and significant inhibitory effects in cell-based and cell-free assays. These compounds represent the most effective ACT/EF inhibitors based on ANPs reported to date.
Review
Biochemistry & Molecular Biology
Kwun Wah Wen, Linlin Wang, Joshua R. Menke, Blossom Damania
Summary: EBV and KSHV, both human gammaherpesviruses with oncogenic properties, are associated with various lymphoproliferative diseases and plasmacytic/plasmablastic neoplasms. These viruses can also infect epithelial cells and cause carcinomas. The pathogenesis of these two viruses is closely linked to the expression of viral proteins.
Article
Pharmacology & Pharmacy
Chloe Borde, Alexandre E. Escargueil, Vincent Marechal
Summary: Epstein-Barr virus (EBV) is a common herpesvirus that persists in most adults and is associated with malignancies. The virus transitions between latent and lytic phases, both contributing to tumor initiation. Recent studies have found that components of the NLRP3 inflammasome are involved in EBV reactivation. This study demonstrates that shikonin, apigenin, and OLT 1177, inhibitors of the NLRP3 inflammasome, effectively inhibit EBV reactivation.
ANTIVIRAL RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Marcela Krecmerova, Pavel Majer, Rana Rais, Barbara S. Slusher
Summary: This review focuses on biologically active phosphonates used in various biomedical applications. The synthesis and modification of prodrugs are discussed, as well as the potential of these compounds in treating viral infections.
FRONTIERS IN CHEMISTRY
(2022)
Review
Microbiology
Dharmendra Kashyap, Samiksha Rele, Pranit Hemant Bagde, Vaishali Saini, Debi Chatterjee, Ajay Kumar Jain, Rajan Kumar Pandey, Hem Chandra Jha
Summary: Cancer is characterized by mutagenic events that disrupt cell signaling and functions. Pathogens, especially Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with human cancer development. Co-infection of these pathogens can lead to gastric cancer by causing DNA damage and dysregulating cellular signaling pathways related to growth, apoptosis, and DNA repair. This review focuses on the oncogenic roles of H. pylori, EBV, and associated signaling cascades in various cancers, providing insights for preventing and treating H. pylori and EBV-associated cancers.
ARCHIVES OF MICROBIOLOGY
(2023)
Article
Virology
Lingtong Huang, Xuan Zhang, Lisha Pang, Peng Sheng, Yanqiu Wang, Fan Yang, Huili Yu, Xiaohan Huang, Yue Zhu, Ning Zhang, Hongliu Cai, Lingling Tang, Xueling Fang
Summary: This study aimed to assess the landscape and clinical features of viral reactivation in the early onset of severe pneumonia in ICU patients. The most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia were cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV). Viral reactivation was associated with an increased risk of mortality.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Immunology
Jing-Rui Zhou, Da-Yu Shi, Rong Wei, Yu Wang, Chen-Hua Yan, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Yu-Qian Sun
Summary: Reactivation of both cytomegalovirus and Epstein-Barr virus is common after hematopoietic stem cell transplantation and is associated with poor outcomes, including lower overall survival and leukemia-free survival rates. Co-reactivation of these viruses is also linked to prolonged viral duration and poor CD4+CD25+ T cell reconstitution post-transplantation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chung-Chun Wu, Ting-Ying Lee, Yu-Jhen Cheng, Der-Yang Cho, Jen-Yang Chen
Summary: Kaempferol efficiently inhibits the reactivation of EBV, making it a potential choice for anti-EBV therapy and cancer prevention.
Article
Chemistry, Medicinal
Karolina Vankova, Dianne T. Keough, Dana Hockova, Luke W. Guddat, Zlatko Janeba
Summary: Twelve N2'-branched acyclic nucleoside phosphonates and bisphosphonates were synthesized as potential inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT). The compounds showed low to modest selectivity for the parasite enzyme over human HGPRT. The effect of different chemical groups/linkers attached to N2' atom on inhibition constants and selectivity was discussed.
Article
Infectious Diseases
Yun Xie, Song Cao, Hui Dong, Hui Lv, Xiaolei Teng, Jiaxiang Zhang, Tao Wang, Xiaoyan Zhang, Yun Qin, Yujing Chai, Luyu Yang, Jun Liu, Ruilan Wang
Summary: This retrospective single-center study found that COVID-19 patients with EBV reactivation had higher rates of tachypnoea, greater decreases in lymphocyte and albumin levels, higher levels of D-dimer and serum calcium, higher rates of CRP and occurrence of respiratory failure, ARDS, and hypoproteinaemia, as well as significantly higher 28-day and 14-day mortality rates compared to patients without EBV reactivation. These patients also received more immuno-supportive treatment.
BMC INFECTIOUS DISEASES
(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
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
Chemistry, Multidisciplinary
Jianyang Han, Jakob Arnold, Christophe Pannecouque, Graciela Andrei, Robert Snoeck, Clemens Richert
Summary: Strongly pairing ethynylpyridone C-nucleosides are being explored as substitutes for thymidine in oligonucleotides. However, the strong lipophilicity of ethynylpyridone has been found to limit its antiviral activity. Two strategies are being pursued to overcome this issue, including replacing the ethynyl group with a cyano group and using less lipophilic amino acid esters in a phosphoramidate prodrug design. These findings contribute to the development of next-generation pyridone C-nucleosides as potential antivirals.
HELVETICA CHIMICA ACTA
(2023)
Article
Biochemistry & Molecular Biology
Zhao-Hui Wen, Meng-Meng Wang, Ling-Yun Li, Piet Herdewijn, Robert Snoeck, Graciela Andrei, Zhao-Peng Liu, Chao Liu
Summary: In this study, the synthesis of lipid prodrugs of beta-D-N4-hydroxycytidine (NHC) and a 3'-fluoro modified NHC analogue was reported, and their antiviral activity against five variants of SARS-CoV-2 was evaluated. The lipid prodrugs showed potent antiviral activity against the tested variants, with comparable or higher EC50 values than remdesivir and molnupiravir. The 3'-F analogue of NHC only exhibited minor antiviral activity against the Omicron variant, while no activity was observed against other variants. The promising antiviral data of the lipid prodrugs suggest their potential as new anti-SARS-CoV-2 drugs.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
M. P. Paramonova, E. S. Gureeva, A. A. Ozerov, R. Snoeck, G. Andrei, D. A. Aleksandrov, A. L. Khandazhinskaya, M. S. Novikov, S. N. Kochetkov
Summary: A new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing various fragments were synthesized and tested for their antiviral activity against human cytomegalovirus. It was found that the compound with a bridge of five methylene groups exhibited high anti-cytomegalovirus activity in vitro.
DOKLADY BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Chemistry, Medicinal
Roberta Bivacqua, Marilia Barreca, Virginia Spano, Maria Valeria Raimondi, Isabella Romeo, Stefano Alcaro, Graciela Andrei, Paola Barraja, Alessandra Montalbano
Summary: Viruses are responsible for causing various pathological conditions, with efforts made to identify selective viral targets for developing efficient therapeutics. Polymerases are attractive targets due to their crucial role in the viral life cycle. This overview focuses on non-nucleoside triazole-based compounds discovered in the past fifteen years as potential viral polymerase inhibitors, highlighting the structure-activity relationships necessary for developing effective antiviral agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Hanna Helena Schalkwijk, Aspasia Georgala, Sarah Gillemot, Arturo Temblador, Dimitri Topalis, Sebastian Wittnebel, Graciela Andrei, Robert Snoeck
Summary: This study conducted long-term follow-up of a patient with immunodeficiency before and after stem cell transplantation, revealing the evolution and frequent reactivation of herpes simplex virus 1 strains. The multidrug resistance phenotype of a novel DNA polymerase mutation was confirmed by gene editing. This research is important for understanding virus evolution and drug resistance mutations in immunodeficient patients.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Pharmacology & Pharmacy
Evelien Vanderlinden, Arnaud Boonen, Sam Noppen, Geert Schoofs, Maya Imbrechts, Nick Geukens, Robert Snoeck, Annelies Stevaert, Lieve Naesens, Graciela Andrei, Dominique Schols
Summary: PRO-2000, a sulfonated polyanionic compound, has anti-SARS-CoV-2 activity by blocking the entry pathway and inhibiting the binding of the S protein to its receptor. It can potentially inhibit a broad range of SARS-CoV-2 variants.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Rui Wang, Annelies Stevaert, Tien Nguyen Truong, Qifei Li, Besir Krasniqi, Benjamin Van Loy, Arnout Voet, Lieve Naesens, Wim Dehaen
Summary: The study investigates the structure-activity relationship of novel coronavirus inhibitors and identifies a class of 1,2,3-triazolo fused triterpenoid compounds with strong antiviral activity against HCoV-229E.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Polina Kamzeeva, Ivan Petushkov, Ekaterina Knizhnik, Robert Snoeck, Yuri Khodarovich, Ekaterina Ryabukhina, Vera Alferova, Artur Eshtukov-Shcheglov, Evgeny Belyaev, Julia Svetlova, Tatiana Vedekhina, Andrey Kulbachinskiy, Anna Varizhuk, Graciela Andrei, Andrey Aralov
Summary: Emerging and re-emerging viruses cause global outbreaks and epidemics, highlighting the need for new antiviral drugs. Researchers synthesized and evaluated nucleoside analogs and their derivatives, finding that one compound had antiviral activity against coronaviruses and specifically inhibited biocondensate formation important for replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Graciela Andrei, Robert Snoeck
Summary: This article discusses the global outbreak of mpox virus (MPXV) since May 2022 and its differences from the traditional mpox virus endemic in Africa. The study explores the genomic changes and drivers of MPXV evolution, as well as the use of vaccines and antivirals developed against smallpox virus in containing the mpox outbreak.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Olga Mineeva-Sangwo, Elisabet Van Loon, Graciela Andrei, Dirk Kuypers, Maarten Naesens, Robert Snoeck
Summary: BK polyomavirus (BKPyV) is a latent human DNA virus in renal tissue that can reactivate and cause polyomavirus-associated nephropathy (PVAN), particularly in kidney transplant recipients. There are currently no specific antivirals for BKPyV, so reducing immunosuppression is the main treatment approach. Mutations in the major capsid protein VP1 of BKPyV can accumulate over time and lead to neutralization escape in kidney transplant recipients. A study found mutations throughout the entire BKPyV genome, including VP1, and these changes should be considered in future approaches for treating BKPyV infection in kidney transplant recipients.
SCIENTIFIC REPORTS
(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)