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22 results on '"El-Kazzi, Priscila"'

4. A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase

Author

Shannon, Ashleigh, Fattorini, Véronique, Sama, Bhawna, Selisko, Barbara, Feracci, Mikael, Falcou, Camille, Gauffre, Pierre, El Kazzi, Priscila, Delpal, Adrien, Decroly, Etienne, Alvarez, Karine, Eydoux, Cécilia, Guillemot, Jean-Claude, Moussa, Adel, Good, Steven S., La Colla, Paolo, Lin, Kai, Sommadossi, Jean-Pierre, Zhu, Yingxiao, Yan, Xiaodong, Shi, Hui, Ferron, François, and Canard, Bruno

Published
2022
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5. ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming

Author

Menzies, Stefanie K., primary, Arinto-Garcia, Raquel, additional, Amorim, Fernanda Gobbi, additional, Cardoso, Iara Aimê, additional, Abada, Camille, additional, Crasset, Thomas, additional, Durbesson, Fabien, additional, Edge, Rebecca J., additional, El-Kazzi, Priscila, additional, Hall, Sophie, additional, Redureau, Damien, additional, Stenner, Richard, additional, Boldrini-França, Johara, additional, Sun, Huan, additional, Roldão, António, additional, Alves, Paula M., additional, Harrison, Robert A., additional, Vincentelli, Renaud, additional, Berger, Imre, additional, Quinton, Loïc, additional, Casewell, Nicholas R., additional, and Schaffitzel, Christiane, additional

Published
2023
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6. ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming

Author

Menzies, Stefanie Kate, primary, Arinto-Garcia, Raquel, additional, Amorim, Fernanda Gobbi, additional, Cardoso, Iara Aime, additional, Abada, Camille, additional, Crasset, Thomas, additional, Durbesson, Fabien, additional, Edge, Rebecca J, additional, El-Kazzi, Priscila, additional, Hall, Sophie, additional, Redureau, Damien, additional, Stenner, Richard, additional, Boldrini-França, Johara, additional, Sun, Huan, additional, Roldão, António, additional, Alves, Paula M, additional, Vincentelli, Renaud, additional, Berger, Imre, additional, Quinton, Loïc, additional, Casewell, Nicholas R, additional, and Schaffitzel, Christiane, additional

Published
2023
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9. ADDovenom : Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming

Author

Menzies, Stefanie K., Arinto-Garcia, Raquel, Amorim, Fernanda Gobbi, Cardoso, Iara Aimê, Abada, Camille, Crasset, Thomas, Durbesson, Fabien, Edge, Rebecca J., El-Kazzi, Priscila, Hall, Sophie, Redureau, Damien, Stenner, Richard, Boldrini-França, Johara, Sun, Huan, Roldão, António, Alves, Paula M., Harrison, Robert A., Vincentelli, Renaud, Berger, Imre, Quinton, Loïc, Casewell, Nicholas R., Schaffitzel, Christiane, Menzies, Stefanie K., Arinto-Garcia, Raquel, Amorim, Fernanda Gobbi, Cardoso, Iara Aimê, Abada, Camille, Crasset, Thomas, Durbesson, Fabien, Edge, Rebecca J., El-Kazzi, Priscila, Hall, Sophie, Redureau, Damien, Stenner, Richard, Boldrini-França, Johara, Sun, Huan, Roldão, António, Alves, Paula M., Harrison, Robert A., Vincentelli, Renaud, Berger, Imre, Quinton, Loïc, Casewell, Nicholas R., and Schaffitzel, Christiane

Abstract

Snakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom—polyclonal antibodies isolated from the plasma of hyperimmunised animals—which is associated with numerous deficiencies. The ADDovenom project seeks to deliver a novel snakebite therapy, through the use of an innovative protein-based scaffold as a next-generation antivenom. The ADDomer is a megadalton-sized, thermostable synthetic nanoparticle derived from the adenovirus penton base protein; it has 60 high-avidity binding sites to neutralise venom toxins. Here, we outline our experimental strategies to achieve this goal using state-of-the-art protein engineering, expression technology and mass spectrometry, as well as in vitro and in vivo venom neutralisation assays. We anticipate that the approaches described here will produce antivenom with unparalleled efficacy, safety and affordability.

Published
2023

11. Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex

Author

Virologie, dI&I I&I-1, Sub Biomol.Mass Spectrometry & Proteom., Sub Structural Biochemistry, Structural Biochemistry, Biomolecular Mass Spectrometry and Proteomics, Hurdiss, Daniel L., El Kazzi, Priscila, Bauer, Lisa, Papageorgiou, Nicolas, Ferron, François P., Donselaar, Tim, Van Vliet, Arno L.W., Shamorkina, Tatiana M., Snijder, Joost, Canard, Bruno, Decroly, Etienne, Brancale, Andrea, Zeev-Ben-Mordehai, Tzviya, Förster, Friedrich, Van Kuppeveld, Frank J.M., Coutard, Bruno, Virologie, dI&I I&I-1, Sub Biomol.Mass Spectrometry & Proteom., Sub Structural Biochemistry, Structural Biochemistry, Biomolecular Mass Spectrometry and Proteomics, Hurdiss, Daniel L., El Kazzi, Priscila, Bauer, Lisa, Papageorgiou, Nicolas, Ferron, François P., Donselaar, Tim, Van Vliet, Arno L.W., Shamorkina, Tatiana M., Snijder, Joost, Canard, Bruno, Decroly, Etienne, Brancale, Andrea, Zeev-Ben-Mordehai, Tzviya, Förster, Friedrich, Van Kuppeveld, Frank J.M., and Coutard, Bruno

Published
2022

12. Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex

Author

Hurdiss, Daniel L., El Kazzi, Priscila, Bauer, Lisa, Papageorgiou, Nicolas, Ferron, François P., Donselaar, Tim, Van Vliet, Arno L.W., Shamorkina, Tatiana M., Snijder, Joost, Canard, Bruno, Decroly, Etienne, Brancale, Andrea, Zeev-Ben-Mordehai, Tzviya, Förster, Friedrich, Van Kuppeveld, Frank J.M., Coutard, Bruno, Virologie, dI&I I&I-1, Sub Biomol.Mass Spectrometry & Proteom., Sub Structural Biochemistry, Structural Biochemistry, Biomolecular Mass Spectrometry and Proteomics, Virologie, dI&I I&I-1, Sub Biomol.Mass Spectrometry & Proteom., Sub Structural Biochemistry, Structural Biochemistry, Biomolecular Mass Spectrometry and Proteomics, Utrecht University [Utrecht], Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Infectious Diseases and Immunology [Utrecht, The Netherlands], Utrecht University [Utrecht]-WHO Collaborating Center for Campylobacter /OIE Reference Laboratory for Campylobacteriosis (Utrecht), European Virus Bioinformatics Center [Jena], Cardiff University, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ferron, François

Subjects
Multidisciplinary, [SDV]Life Sciences [q-bio], viruses, SciAdv r-articles, [SDV] Life Sciences [q-bio], Structural Biology, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [CHIM.CRIS]Chemical Sciences/Cristallography, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biomedicine and Life Sciences, [CHIM.CRIS] Chemical Sciences/Cristallography, General, Research Article
Abstract

Description, Researchers show how the antidepressant drug fluoxetine targets a viral protein and inhibits viral replication., Enteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus replication. Drug repurposing screens identified 2C-targeting compounds such as fluoxetine and dibucaine, but how they inhibit 2C is unknown. Here, we present a crystal structure of the soluble and monomeric fragment of coxsackievirus B3 2C protein in complex with (S)-fluoxetine (SFX), revealing an allosteric binding site. To study the functional consequences of SFX binding, we engineered an adenosine triphosphatase (ATPase)–competent, hexameric 2C protein. Using this system, we show that SFX, dibucaine, HBB [2-(α-hydroxybenzyl)-benzimidazole], and guanidine hydrochloride inhibit 2C ATPase activity. Moreover, cryo–electron microscopy analysis demonstrated that SFX and dibucaine lock 2C in a defined hexameric state, rationalizing their mode of inhibition. Collectively, these results provide important insights into 2C inhibition and a robust engineering strategy for structural, functional, and drug-screening analysis of 2C proteins.

Published
2022
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14. Structure–function analysis of the nsp14 N7–guanine methyltransferase reveals an essential role inBetacoronavirusreplication

Author

Ogando, Natacha S., primary, El Kazzi, Priscila, additional, Zevenhoven-Dobbe, Jessika C., additional, Bontes, Brenda W., additional, Decombe, Alice, additional, Posthuma, Clara C., additional, Thiel, Volker, additional, Canard, Bruno, additional, Ferron, François, additional, Decroly, Etienne, additional, and Snijder, Eric J., additional

Published
2021
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15. A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase

Author

Canard, Bruno, primary, Shannon, Ashleigh, additional, Fattorini, Veronique, additional, Sama, Bhawna, additional, Selisko, Barbara, additional, Feracci, Mikael, additional, Falcou, Camille, additional, Gauffre, Pierre, additional, El-Kazzi, Priscila, additional, Decroly, Etienne, additional, Alvarez, Karine, additional, Eydoux, Cecilia, additional, Guillemot, Jean-Claude, additional, Moussa, Adel, additional, Good, Steven, additional, Colla, Paolo La, additional, Lin, Kai, additional, Sommadossi, Jean-Pierre, additional, Zhu, Yingxao, additional, Yan, Xiaodong, additional, Shi, Hui, additional, Ferron, Francois, additional, and Delpal, Adrien, additional

Published
2021
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16. Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes the hexameric complex

Author

Hurdiss, Daniel L., primary, El Kazzi, Priscila, additional, Bauer, Lisa, additional, Papageorgiou, Nicolas, additional, Ferron, François P., additional, Donselaar, Tim, additional, van Vliet, Arno L.W., additional, Canard, Bruno, additional, Decroly, Etienne, additional, Brancale, Andrea, additional, Zeev-Ben-Mordehai, Tzviya, additional, Förster, Friedrich, additional, van Kuppeveld, Frank J.M, additional, and Coutard, Bruno, additional

Published
2021
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19. Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner

Author

Bauer, L., Manganaro, Roberto, Zonsics, Birgit, Strating, J.R.P.M., El Kazzi, Priscila, Lorenzo Lopez, Moira, Ulferts, R., van Hoey, Clara, Mate, Maria J., Langer, Thierry, Coutard, Bruno, Brancale, Andrea, van Kuppeveld, F.J.M., LS Virologie, dI&I I&I-1, Department of Infectious Diseases and Immunology [Utrecht, The Netherlands], Utrecht University [Utrecht]-WHO Collaborating Center for Campylobacter /OIE Reference Laboratory for Campylobacteriosis (Utrecht), School of Pharmacy and Pharmaceutical Sciences [Cardiff, UK], Cardiff University, Architecture et fonction des Macromolécules Biologiques - UMR 6098 (AFMB), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Department of Pharmaceutical Chemistry [Vienna, Austria], University of Vienna [Vienna], Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), coutard, bruno, LS Virologie, and dI&I I&I-1

Subjects
Models, Molecular, 0301 basic medicine, Drug, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Protein Conformation, Viral protein, media_common.quotation_subject, viruses, 030106 microbiology, Viral Nonstructural Proteins, medicine.disease_cause, Article, enteroviruses, law.invention, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, law, Fluoxetine, medicine, Humans, Homology modeling, virus replication, media_common, Enterovirus D, Human, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Structure, drug repurposing, Chemistry, molecular modeling, Drug Repositioning, virus diseases, Virology, antiviral, Enterovirus B, Human, 3. Good health, Drug repositioning, 030104 developmental biology, Infectious Diseases, Viral replication, Structural Homology, Protein, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Recombinant DNA, Enterovirus, Carrier Proteins, HeLa Cells, Protein Binding, medicine.drug
Abstract

International audience; Enteroviruses (family Picornaviridae) comprise a large group of human pathogens against which no licensed antiviral therapy exists. Drug-repurposing screens uncovered the FDA-approved drug fluoxetine as a replication inhibitor of enterovirus B and D species. Fluoxetine likely targets the nonstructural viral protein 2C, but detailed mode-of-action studies are missing because structural information on 2C of fluoxetine-sensitive enteroviruses is lacking. We here show that broad-spectrum anti-enteroviral activity of fluoxetine is stereospecific concomitant with binding to recombinant 2C. (S)-Fluoxetine inhibits with a 5-fold lower 50% effective concentration (EC50) than racemic fluoxetine. Using a homology model of 2C of the fluoxetine-sensitive enterovirus coxsackievirus B3 (CVB3) based upon a recently elucidated structure of a fluoxetine-insensitive enterovirus, we predicted stable binding of (S)-fluoxetine. Structure-guided mutations disrupted binding and rendered coxsackievirus B3 (CVB3) resistant to fluoxetine. The study provides new insights into the anti-enteroviral mode-of-action of fluoxetine. Importantly, using only (S)-fluoxetine would allow for lower dosing in patients, thereby likely reducing side effects.

Published
2019
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20. Fluoxetine inhibits enterovirus replication by targeting the viral 2C protein in a stereospecific manner

Author

LS Virologie, dI&I I&I-1, Bauer, L., Manganaro, Roberto, Zonsics, Birgit, Strating, J.R.P.M., El Kazzi, Priscila, Lorenzo Lopez, Moira, Ulferts, R., van Hoey, Clara, Mate, Maria J., Langer, Thierry, Coutard, Bruno, Brancale, Andrea, van Kuppeveld, F.J.M., LS Virologie, dI&I I&I-1, Bauer, L., Manganaro, Roberto, Zonsics, Birgit, Strating, J.R.P.M., El Kazzi, Priscila, Lorenzo Lopez, Moira, Ulferts, R., van Hoey, Clara, Mate, Maria J., Langer, Thierry, Coutard, Bruno, Brancale, Andrea, and van Kuppeveld, F.J.M.

Published
2019

21. [How do 2'-O-methylations within Human Immunodeficiency Virus type 1 (HIV-1) genome regulate its replication?]

Author

Decombe A, El-Kazzi P, Nisole S, and Decroly É

Subjects
Humans, Methylation, HIV Infections virology, HIV Infections genetics, RNA, Viral genetics, RNA, Viral metabolism, HIV-1 physiology, HIV-1 genetics, Virus Replication genetics, Virus Replication physiology, Genome, Viral physiology
Abstract

The genomic RNA of HIV-1 is modified by epitranscriptomic modifications, including 2'-O-methylations, which are found on 17 internal positions. These methylations are added by the cellular methyltransferase FTSJ3, and have pro-viral effects, since they shield the viral genome from the detection by the innate immune sensor MDA5. In turn, the production of interferons by infected cells is reduced, limiting the expression of interferon-stimulated genes (ISGs) with antiviral activities. Moreover, 2'-O-methylations protect the HIV-1 genome from its degradation by ISG20, an interferon-induced exonuclease. Conversely, these methylations also exhibit antiviral effects, as they impede reverse-transcription in vitro or in quiescent cells, which are known to contain low nucleotide concentrations. Altogether, these observations suggest a balance between the proviral effect of 2'-O-methylations, related to the protection of the viral genome from detection by MDA5 and degradation by ISG20, and the antiviral effect, associated with the negative impact of 2'-O-methylations on the viral replication. These findings pave the way for further optimization of therapeutic RNA, by selective methylation of specific nucleotides., (© 2024 médecine/sciences – Inserm.)

Published
2024
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22. Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner.

Author

Bauer L, Manganaro R, Zonsics B, Strating JRPM, El Kazzi P, Lorenzo Lopez M, Ulferts R, van Hoey C, Maté MJ, Langer T, Coutard B, Brancale A, and van Kuppeveld FJM

Subjects
Carrier Proteins chemistry, Carrier Proteins genetics, Drug Repositioning, Enterovirus B, Human drug effects, Enterovirus D, Human drug effects, HeLa Cells, Humans, Models, Molecular, Molecular Structure, Mutation, Protein Binding, Protein Conformation, Structural Homology, Protein, Viral Nonstructural Proteins chemistry, Viral Nonstructural Proteins genetics, Carrier Proteins metabolism, Enterovirus B, Human physiology, Enterovirus D, Human physiology, Fluoxetine pharmacology, Viral Nonstructural Proteins metabolism, Virus Replication drug effects
Abstract

Enteroviruses (family Picornaviridae ) comprise a large group of human pathogens against which no licensed antiviral therapy exists. Drug-repurposing screens uncovered the FDA-approved drug fluoxetine as a replication inhibitor of enterovirus B and D species. Fluoxetine likely targets the nonstructural viral protein 2C, but detailed mode-of-action studies are missing because structural information on 2C of fluoxetine-sensitive enteroviruses is lacking. We here show that broad-spectrum anti-enteroviral activity of fluoxetine is stereospecific concomitant with binding to recombinant 2C. ( S )-Fluoxetine inhibits with a 5-fold lower 50% effective concentration (EC 50 ) than racemic fluoxetine. Using a homology model of 2C of the fluoxetine-sensitive enterovirus coxsackievirus B3 (CVB3) based upon a recently elucidated structure of a fluoxetine-insensitive enterovirus, we predicted stable binding of ( S )-fluoxetine. Structure-guided mutations disrupted binding and rendered coxsackievirus B3 (CVB3) resistant to fluoxetine. The study provides new insights into the anti-enteroviral mode-of-action of fluoxetine. Importantly, using only ( S )-fluoxetine would allow for lower dosing in patients, thereby likely reducing side effects.

Published
2019
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