Article
Pharmacology & Pharmacy
Sook Kwan Brown, Yeu-Yang Tseng, Ammar Aziz, Mariana Baz, Ian G. Barr
Summary: This study tested 3425 influenza B viruses collected from the Asia-Pacific region against four registered neuraminidase inhibitors (NAIs). It identified 45 influenza B viruses with reduced susceptibility to one or more NAIs, including some with newly identified neuraminidase mutations. The study highlights the potential impact of these mutations on the clinical effectiveness of NAIs in treating influenza B infections in humans.
ANTIVIRAL RESEARCH
(2022)
Article
Virology
Xiaoxue He, Fan Yang, Yan Wu, Jia Lu, Xiao Gao, Xuerui Zhu, Jie Yang, Shuwen Liu, Gengfu Xiao, Xiaoyan Pan
Summary: This study identifies tanshinone I and tanshinone IIA as candidate compounds with broad-spectrum antiviral activities against various viruses, including bandaviruses, influenza A virus, and arenavirus. The antiviral activity is achieved by inhibiting the endonuclease activity involved in the cap-snatching process.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Luca Zinzula, Angela Maria Mereu, Massimiliano Orsini, Christine Seeleitner, Andreas Bracher, Istvan Nagy, Wolfgang Baumeister
Summary: This study established a split-green fluorescent protein method to probe the assembly of Ebola virus and Marburg virus VP35 coiled-coil. Screening of a small compound library led to the identification of two inhibitors, validating the importance of VP35 coiled-coil as an antiviral target.
Article
Multidisciplinary Sciences
Jingru Fang, Guillaume Castillon, Sebastien Phan, Sara McArdle, Chitra Hariharan, Aiyana Adams, Mark H. Ellisman, Ashok A. Deniz, Erica Ollmann Saphire
Summary: Ebola virus infection induces the formation of biomolecular condensates called viral factories, which coordinate viral transcription, replication, and assembly. The authors characterized the phase separation properties and internal structures of intracellular viral factories induced by Ebola virus, and correlated these properties to important steps of viral biogenesis.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Diego J. Paez-Moscoso, David Ho, Lili Pan, Katie Hildebrand, Kristi L. Jensen, Michaella J. Levy, Laurence Florens, Peter Baumann
Summary: Most eukaryotes maintain telomeres using a specialized reverse transcriptase. This study found that Thc1, Bmc1, and Pof8 form a complex in fission yeast and are involved in telomerase biogenesis, which is crucial for telomerase activity and telomere length maintenance.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Silvana Vasile, Katarina Roos
Summary: In this study, density functional theory (DFT) was used to predict the binding free energies of metalloenzyme fragment-like inhibitors. By introducing automated docking, high affinity inhibitors were identified. This methodology provides a fast and predictive tool for the identification of key features of metalloenzyme MBGs, which can be useful for the design of new and efficient drugs targeting these ubiquitous proteins.
Review
Biochemistry & Molecular Biology
Joon Park, Noe Baruch-Torres, Y. Whitney Yin
Summary: Human mitochondrial DNA (mtDNA) is a circular double-stranded DNA, responsible for encoding subunits of the electron transfer chain and essential RNAs for mitochondrial protein translation. The minimal mtDNA replisome consists of Twinkle, DNA polymerase gamma, and mitochondrial single-stranded DNA-binding protein. Both mitochondrial RNA transcription and DNA replication machineries are intertwined and regulate mtDNA copy numbers, cellular energy supplies, and cellular metabolism. This review focuses on the structural aspects of the mechanisms governing these pathways, and the mtDNA diseases caused by mutations in transcription and replication machineries. Additionally, it discusses the adverse effects of antiviral drugs on mitochondrial DNA and RNA polymerases, as well as potential structural approaches for developing less toxic nucleoside reverse transcriptase inhibitors and ribonucleoside analogs.
Article
Oncology
Jessica Marinello, Andrea Arleo, Marco Russo, Maria Delcuratolo, Francesca Ciccarelli, Yves Pommier, Giovanni Capranico
Summary: This study used molecular, genetic, and bioinformatic approaches to investigate the mechanism of micronuclei formation induced by TOP1 poisons in different cancer cells. The results revealed an immune signaling mechanism activated by TOP1 poisons, which is often impaired in human small-cell lung cancer tumors.
BRITISH JOURNAL OF CANCER
(2022)
Article
Plant Sciences
Wenzhong Lin, Qingchen Zha, Wenwen Zhang, Guanwei Wu, Fei Yan, Zujian Wu, Zhenguo Du
Summary: This study demonstrates the inhibitory effects of antiviral compounds targeting cap-snatching of influenza virus on the transcription of rice stripe virus. The results suggest that these compounds could serve as starting points in developing antivirals against RSV or related plant viruses.
PHYTOPATHOLOGY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Liuke Sun, Huihui Kong, Mengmeng Yu, Zhenyu Zhang, Haili Zhang, Lei Na, Yuxing Qu, Yuan Zhang, Hualan Chen, Xiaojun Wang
Summary: Species differences in ANP32A/B restrict avian influenza virus in mammalian cells. Adaptive mutations, such as PB2-E627K, are required for efficient replication of avian influenza viruses in mammals. We found that NS2 protein promotes avian vRNP assembly and enhances interactions with mammalian ANP32A/B, overcoming the restriction. Disrupting the conserved SUMO-interacting motif (SIM) in NS2 impairs virus replication and pathogenicity in mammals, indicating NS2 as a cofactor in the adaptation process of avian influenza virus to mammals.
Article
Microbiology
Leo Y. Y. Lee, Jie Zhou, Paulina Koszalka, Rebecca Frise, Rubaiyea Farrukee, Keiko Baba, Shahjahan Miah, Takao Shishido, Monica Galiano, Takashi Hashimoto, Shinya Omoto, Takeki Uehara, Edin J. Mifsud, Neil Collinson, Klaus Kuhlbusch, Barry Clinch, Steffen Wildum, Wendy S. Barclay, Aeron C. Hurt
Summary: This study evaluated the fitness of influenza viruses with reduced baloxavir susceptibility in ferrets. The results showed that these viruses had slightly reduced within-host fitness compared to wild-type viruses, but significant differences in between-host fitness, suggesting a compromised transmission ability.
Article
Chemistry, Medicinal
Ruibin Liu, Shaoqi Zhan, Ye Che, Jana Shen
Summary: This study verifies the reactivity hypothesis of front pocket (FP) N-terminal cap (Ncap) cysteine in kinases through CpHMD simulations, and offers a systematic understanding of the cysteine structure-reactivity relationship.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Virology
Jesse D. Pyle, Sean P. J. Whelan
Summary: Arenaviruses initiate infection by delivering a transcriptionally competent ribonucleoprotein complex into host cells. The interaction between the large RNA-dependent RNA polymerase (L) and nucleoprotein (NP) plays a central role in arenavirus gene expression. Purification of recombinant functional RNPs from mammalian cells allows for further biochemical analysis of the L and NP proteins interaction.
JOURNAL OF VIROLOGY
(2021)
Article
Cell Biology
Takaaki Yasuhara, Reona Kato, Motohiro Yamauchi, Yuki Uchihara, Lee Zou, Kiyoshi Miyagawa, Atsushi Shibata
Summary: RAP80 is identified as a factor that suppresses the vulnerability of single-stranded DNA (ssDNA) in R-loops during DNA double-strand break (DSB) repair, preventing genomic abnormalities caused by harmful R-loop processing.
Article
Microbiology
Saori Suzuki, Cong Thanh Nguyen, Ayako Ogata-Nakahara, Akihiro Shibata, Hiroyuki Osaka, Hirohito Ishigaki, Masatoshi Okamatsu, Yoshihiro Sakoda, Hiroshi Kida, Kazumasa Ogasawara, Yasushi Itoh
Summary: The study revealed that H7N9 avian influenza virus Dk/HE29-22 caused severe symptoms and pneumonia in macaques, but treatment with baloxavir significantly reduced viral titers in the primates. Additionally, interferon levels were highest in the baloxavir-treated group, suggesting a potential therapeutic benefit in reducing influenza severity.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biology
Celine Dard, Christopher Swale, Marie-Pierre Brenier-Pinchart, Dayana C. Farhat, Valeria Bellini, Marie Gladys Robert, Dominique Cannella, Herve Pelloux, Isabelle Tardieux, Mohamed-Ali Hakimi
Summary: Discovery of the protein BCLA/MAG2 as a specific marker for bradyzoite and cyst envelope in T. gondii has been achieved through genetically engineered parasites. By using lab mice as models, researchers have confirmed that BCLA/MAG2 can stimulate antibody production recognizing bradyzoite and cyst structure. An ELISA assay based on a bacterially produced BCLA recombinant polypeptide has been designed and validated using sera from mice and human patients with toxoplasmosis, showing promising results for detection of persistent T. gondii infection.
Article
Biochemistry & Molecular Biology
Olivier Terrier, Sebastien Dilly, Andres Pizzorno, Dominika Chalupska, Jana Humpolickova, Evzen Boura, Francis Berenbaum, Stephane Quideau, Bruno Lina, Bruno Feve, Frederic Adnet, Michele Sabbah, Manuel Rosa-Calatrava, Vincent Marechal, Julien Henri, Anny Slama-Schwok
Summary: The study investigates the efficacy of naproxen as an antiviral drug against SARS-CoV-2, finding that it can inhibit viral replication in infected cells and protect respiratory epithelium from damage. Compared to other tested drugs, naproxen combines antiviral and anti-inflammatory properties.
Article
Biochemistry & Molecular Biology
Raoul Manuel, Michelle de Souza Lima, Sebastien Dilly, Sylvain Daunay, Patricia Abbe, Elodie Pramil, Stephanie Solier, Fabienne Guillaumond, Sarah-Simha Tubiana, Alexandre Escargueil, Joao Antonio Pegas Henriques, Nathalie Ferrand, Irene Erdelmeier, Jean-Luc Boucher, Gildas Bertho, Israel Agranat, Stephane Rocchi, Michele Sabbah, Anny Slama Schwok
Summary: Research on specific inhibition of NADPH oxidases (NOX) and NO-synthases (NOS) has attracted great pharmacological interest due to their association with redox stress in tumor cells. The study demonstrated that isolated 2'- and 3'-phosphate isomers of the NADPH analogue NS1 improved the specificity of inhibition by distinguishing between isomeric derivatives. The 2'-phosphate isomer of NS1 showed more pronounced effects on NOS and NOX-dependent physiological responses, with docking and molecular dynamics simulations explaining the specificity at the NADPH site of NOX and NOS.
Article
Biology
Dayana C. Farhat, Matthew W. Bowler, Guillaume Communie, Dominique Pontier, Lucid Belmudes, Caroline Mas, Charlotte Corrao, Yohann Coute, Alexandre Bougdour, Thierry Lagrange, Mohamed-Ali Hakimi, Christopher Swale
Summary: Proper 3' end processing of mRNAs is crucial for gene expression regulation. This study in T. gondii identifies an m6A-dependent 3'end polyadenylation acting as a transcriptional barrier. Loss of m6A leads to aberrantly elongated chimeric mRNAs due to impaired transcriptional termination. Overall, the results highlight a regulatory mechanism coupling m6A metabolism to cleavage and polyadenylation processes, serving as a guardian against aberrant transcriptional read-throughs.
Review
Virology
Daniel Kolakofsky, Philippe Le Mercier, Machiko Nishio, Martin Blackledge, Thibaut Crepin, Rob W. H. Ruigrok
Summary: VSV and SeV are members of the Mononegavirales order, studying these viruses can provide insights into their genetic information expression and RNA synthesis processes, as well as the characteristics of their nucleocapsid, helping to establish a unified model based on commonalities among these viruses.
Review
Microbiology
Olivier Terrier, Mustapha Si-Tahar, Mariette Ducatez, Christophe Chevalier, Andres Pizzorno, Ronan Le Goffic, Thibaut Crepin, Gaelle Simon, Nadia Naffakh
Summary: The development of vaccines against SARS-CoV-2 was a remarkable achievement, but it also highlighted weaknesses in global pandemic response and gaps in our knowledge of coronaviruses and influenza viruses. By reviewing current knowledge of these viruses, common research challenges were identified, emphasizing the need for multidisciplinary approaches and technological innovations to improve preparedness for future pandemics.
Article
Biochemistry & Molecular Biology
Antoine Guillon, Deborah Brea-Diakite, Adeline Cezard, Alan Wacquiez, Thomas Baranek, Jerome Bourgeais, Frederic Picou, Virginie Vasseur, Lea Meyer, Christophe Chevalier, Adrien Auvet, Jose M. Carballido, Lydie Nadal Desbarats, Florent Dingli, Andrei Turtoi, Audrey Le Gouellec, Florence Fauvelle, Amelie Donchet, Thibaut Crepin, Pieter S. Hiemstra, Christophe Paget, Damarys Loew, Olivier Herault, Nadia Naffakh, Ronan Le Goffic, Mustapha Si-Tahar
Summary: Research has shown that influenza virus infection causes significant changes in lung metabolism, leading to the accumulation of succinate in respiratory fluids. Succinate exhibits powerful antiviral activity by inhibiting influenza virus replication and reducing metabolic disruptions and inflammatory responses. Administering succinate intranasally to mice reduces viral loads in the lungs and improves survival rates. The antiviral mechanism involves succinylation of viral nucleoproteins, which alters their interactions with viral RNA.
Article
Cell Biology
Christopher Swale, Valeria Bellini, Matthew W. Bowler, Nardella Flore, Marie-Pierre Brenier-Pinchart, Dominique Cannella, Lucid Belmudes, Caroline Mas, Yohann Coute, Fabrice Laurent, Artur Scherf, Alexandre Bougdour, Mohamed-Ali Hakimi
Summary: The Apicomplexa, a phylum of single-celled protozoa, cause severe parasitic diseases in humans and animals. Current therapeutics are limited by their efficacy and resistance. In this study, altiratinib, originally developed for glioblastoma, is identified as a potential drug candidate with broad spectrum activity against apicomplexans. Altiratinib specifically targets the TgPRP4K of T. gondii and inhibits the development of intracellular parasites. The molecular basis of the inhibitory mechanism and species selectivity is further elucidated.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Julien Henri, Laetitia Minder, Kevin Mohanasundaram, Sebastien Dilly, Anne Goupil-Lamy, Carmelo Di Primo, Anny Slama Schwok
Summary: This study identified new ligands of the nucleoprotein N of SARS-CoV-2 by in silico screening, using a refined Alphafold model of N and molecular dynamic simulations. The ligands, neuropeptides like substance P and enkephalin, impeded RNA binding to N and potentially altered the physiological roles of these neuropeptides. It was suggested that N may link viral replication and long COVID-19 symptoms, and targeted antivirals against N could improve patients' health.
Article
Biochemistry & Molecular Biology
Stephanie Solier, Michele Mondini, Lydia Meziani, Arnaud Jacquel, Catherine Lacout, Tom Vanden Berghe, Yvon Jule, Jean-Claude Martinou, Gerard Pierron, Julie Riviere, Marc Deloger, Corinne Dupuy, Anny Slama-Schwok, Nathalie Droin, Peter Vandenabeele, Patrick Auberger, Eric Deutsch, Jamel El-Benna, Pham My-Chan Dang, Eric Solary
Summary: Circulating monocytes are recruited to damaged tissues to generate macrophages that modulate disease progression. Activation of caspase-3 and caspase-7, located near mitochondria, is involved in the generation of monocyte-derived macrophages stimulated by Colony-stimulating factor-1 (CSF-1). A non-conventional pathway that involves caspases and activates NOX2 is responsible for CSF1-driven monocyte differentiation, and targeting this pathway may have therapeutic implications for modulating macrophage polarization in damaged tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Virology
Guy Schoehn, Florian Chenavier, Thibaut Crepin
Article
Microbiology
Shruthi Krishnamurthy, Parag Maru, Yifan Wang, Mebratu A. Bitew, Debanjan Mukhopadhyay, Yoshiki Yamaryo-Botte, Tatiana C. Paredes-Santos, Lamba O. Sangare, Christopher Swale, Cyrille Y. Botte, Jeroen P. J. Saeij
Summary: This study identified several Toxoplasma genes important for parasite fitness in human cells stimulated with interferon gamma through a genome-wide loss-of-function screen. Knockout of these genes confirmed their importance for parasite growth in interferon gamma-stimulated human cells. Three of these genes showed homology to GRA32, localized to dense granules, and coimmunoprecipitated with each other and GRA32, indicating they might form a complex. Deletion of individual members of this complex led to early parasite egress in interferon gamma-stimulated cells, highlighting the importance of preventing early egress for Toxoplasma fitness in human cells stimulated with interferon gamma.
Review
Cell Biology
Christopher Swale, Mohamed-Ali Hakimi
Summary: The 3'-end processing of mRNA is a co-transcriptional process that involves a complex composed of cleavage and polyadenylation specificity factors (CPSFs) to recognize cis-sequence elements on nascent mRNA and carry out cleavage and polyadenylation reactions. Recent studies have provided a mechanistic understanding of this machinery in yeast or metazoans, and the discovery of small molecule inhibitors of CPSF function has stimulated interest in studying this machinery in Apicomplexa. The CPSF complex integrates a novel reader of the N6-methyladenosine (m6A) in these organisms and bridges m6A metabolism to transcription termination.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Article
Biochemistry & Molecular Biology
Sebastien Dilly, Miguel Romero, Stephanie Solier, Olivier Feron, Chantal Dessy, Anny Slama Schwok
Summary: ROS in cancer cells play a crucial role in regulating cell death, stemness maintenance, and metabolic reprogramming, which are associated with resistance to chemo/immunotherapy. This paper introduces new inhibitors of NADPH oxidase (NOX), which is important in the tumor microenvironment. One of the inhibitors, called Nanoshutter-1 (NS1), decreases tumor-promoting M2 macrophages in human blood monocytes. NS1 disrupts the NOX2 complex in the macrophages' membrane and mitochondria, leading to vasodilation of blood vessels and potential reduction of hypoxia. By targeting specific cells, NOX2-specific inhibitors could provide precision therapies.
Article
Microbiology
Tatiana C. Paredes-Santos, Mebratu A. Bitew, Christopher Swale, Felipe Rodriguez, Shruthi Krishnamurthy, Yifan Wang, Parag Maru, Lamba Omar Sangare, Jeroen P. J. Saeij
Summary: The study reveals that the proteins GRA17 and GRA23 are essential for the parasite Toxoplasma gondii to acquire nutrients by crossing the vacuole membrane. By conducting a screen in parasites lacking the GRA17 gene, multiple other genes were identified to be critical for the proper localization of dense granule proteins, including GRA17 and GRA23. These findings highlight the importance of these proteins for the parasite's survival and fitness.