Piri Keşif Aracı

Özet Ek Bilgiler

Kaydet

Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.

DOI : 10.1016/j.antiviral.2020.104762

Anahtar Kelimeler : SARS-CoV-2, COVID-19, 2019-nCoV, Chloroquine, Antiviral

ISSN: 0166-3542
Cilt: 177
Sayfa: 104762

Sınıflandırma :

Biyotıp %64

İlaç Direnci %38

Tropik ilaç %27

2

In between: Gypsy in Drosophila melanogaster Reveals New Insights into Endogenous Retrovirus Evolution

Dergi Makalesi

Kaynak 1:

Directory of Open Access Journals (DOAJ)

Kaynak 2:

MDPI

Dergi:

Viruses

Yazar(lar) :

Franck Touret , François Guiguen , Timothy Greenland , Christophe Terzian

Yıl :

2014

Franck Touret

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Retroviruses are RNA viruses that are able to synthesize a DNA copy of their genome and insert it into a chromosome of the host cell. Sequencing of different eukaryote genomes has revealed the presence of many such endogenous retroviral sequences. The mechanisms by which these retroviral sequences have colonized the genome are still unknown, and the endogenous retrovirus gypsy of Drosophila melanogaster is a powerful experimental model for deciphering this process in vivo. Gypsy is expressed in a layer of somatic cells, and then transferred into the oocyte by an unknown mechanism. This critical step is the start of the endogenization process. Moreover gypsy has been shown to have infectious properties, probably due to its envelope gene acquired from a baculovirus. Recently we have also shown that gypsy maternal transmission is reduced in the presence of the endosymbiotic bacterium Wolbachia. These studies demonstrate that gypsy is a unique and powerful model for understanding the endogenization of retroviruses.

Kaynak 1:

https://doi.org/10.3390/v6124914 arayıcılığı görüntüle.
Kaynak 2:

http://dx.doi.org/10.3390/v6124914 arayıcılığı görüntüle.

DOI : 10.3390/v6124914

Anahtar Kelimeler : gypsy, endogenization, piRNA silencing, Drosophila, Wolbachia

ISSN: 1999-4915
Cilt: 6
Sayı: 12
Sayfa: 4914 - 4925

Sınıflandırma :

Biyotıp %95

Viroloji %78

3

Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone.

Dergi Makalesi

Kaynak 1:

PubMed

Kaynak 2:

Directory of Open Access Journals (DOAJ)

Kaynak 3:

Taylor and Francis

Dergi:

Emerg Microbes Infect

Yazar(lar) :

Franck Touret , Magali Gilles , Raphaelle Klitting , Fabien Aubry , Xavier de Lamballerie , Antoine Nougairède

Yıl :

2018

Franck Touret

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Zika virus (ZIKV) has recently become dispersed throughout the tropics and sub-tropics, causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. In this study, we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared different constructs and confirmed the need to modify the cleavage site between the pre-peptide and prM protein. Genotypic characterization of the chimeras indicated that the emergence of compensatory mutations in the E protein was required to restore viral replicative fitness. Using an immunocompromised mouse model, we demonstrated that mice infected with the chimeric virus produced levels of neutralizing antibodies that were close to those observed following infection with ZIKV. Furthermore, pre-immunized mice were protected against viscerotropic and neuroinvasive disease following challenge with a heterologous ZIKV strain. These data provide a sound basis for the future development of this ZIKV vaccine candidate.

Kaynak 1:

https://www.ncbi.nlm.nih.gov/pubmed/19516034 arayıcılığı görüntüle.
Kaynak 2:

https://doi.org/10.1038/s41426-018-0161-7 arayıcılığı görüntüle.
Kaynak 3:

http://dx.doi.org/10.1038/s41426-018-0161-7 arayıcılığı görüntüle.

DOI : 10.1038/s41426-018-0161-7

Sınıflandırma :

Biyotıp %100

Viroloji %100

4

Prolonged Infectivity of SARS-CoV-2 in Fomites

Dergi Makalesi

Kaynak :

Directory of Open Access Journals (DOAJ)

Dergi:

Emerging Infectious Diseases

Yazar(lar) :

Boris Pastorino , Franck Touret , Magali Gilles , Xavier de Lamballerie , Rémi N. Charrel

Yıl :

2020

Franck Touret

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.

DOI : 10.3201/eid2609.201788

Anahtar Kelimeler : COVID-19, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, 2019 coronavirus disease, zoonoses

Cilt: 26
Sayı: 9
Sayfa: 2256 - 2257

5

Heat Inactivation of Different Types of SARS-CoV-2 Samples: What Protocols for Biosafety, Molecular Detection and Serological Diagnostics?

Dergi Makalesi

Kaynak 1:

Directory of Open Access Journals (DOAJ)

Kaynak 2:

MDPI

Dergi:

Viruses

Yazar(lar) :

Boris Pastorino , Franck Touret , Magali Gilles , Xavier de Lamballerie , Remi N. Charrel

Yıl :

2020

Franck Touret

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Standard precautions to minimize the risk of SARS-CoV-2 transmission implies that infected cell cultures and clinical specimens may undergo some sort of inactivation to reduce or abolish infectivity. We evaluated three heat inactivation protocols (56 °C-30 min, 60 °C-60 min and 92 °C-15 min) on SARS-CoV-2 using (i) infected cell culture supernatant, (ii) virus-spiked human sera (iii) and nasopharyngeal samples according to the recommendations of the European norm NF EN 14476-A2. Regardless of the protocol and the type of samples, a 4 Log10 TCID50 reduction was observed. However, samples containing viral loads > 6 Log10 TCID50 were still infectious after 56 °C-30 min and 60 °C-60 min, although infectivity was < 10 TCID50. The protocols 56 °C-30 min and 60 °C-60 min had little influence on the RNA copies detection, whereas 92 °C-15 min drastically reduced the limit of detection, which suggests that this protocol should be avoided for inactivation ahead of molecular diagnostics. Lastly, 56 °C-30 min treatment of serum specimens had a negligible influence on the results of IgG detection using a commercial ELISA test, whereas a drastic decrease in neutralizing titers was observed.

Kaynak 1:

https://doi.org/10.3390/v12070735 arayıcılığı görüntüle.
Kaynak 2:

http://dx.doi.org/10.3390/v12070735 arayıcılığı görüntüle.

DOI : 10.3390/v12070735

Anahtar Kelimeler : SARS-CoV-2, coronavirus, heat inactivation, COVID-19, serology, ELISA

ISSN: 1999-4915
Cilt: 12
Sayı: 735
Sayfa: 735

6

Evaluation of Chemical Protocols for Inactivating SARS-CoV-2 Infectious Samples

Dergi Makalesi

Kaynak 1:

Directory of Open Access Journals (DOAJ)

Kaynak 2:

MDPI

Dergi:

Viruses

Yazar(lar) :

Boris Pastorino , Franck Touret , Magali Gilles , Lea Luciani , Xavier de Lamballerie , Remi N. Charrel

Yıl :

2020

Franck Touret

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Clinical samples collected in coronavirus disease 19 (COVID-19), patients are commonly manipulated in biosafety level 2 laboratories for molecular diagnostic purposes. Here, we tested French norm NF-EN-14476+A2 derived from European standard EN-14885 to assess the risk of manipulating infectious viruses prior to RNA extraction. SARS-CoV-2 cell-culture supernatant and nasopharyngeal samples (virus-spiked samples and clinical samples collected in COVID-19 patients) were used to measure the reduction of infectivity after 10 minute contact with lysis buffer containing various detergents and chaotropic agents. A total of thirteen protocols were evaluated. Two commercially available formulations showed the ability to reduce infectivity by at least 6 log 10, whereas others proved less effective.

Kaynak 1:

https://doi.org/10.3390/v12060624 arayıcılığı görüntüle.
Kaynak 2:

http://dx.doi.org/10.3390/v12060624 arayıcılığı görüntüle.

DOI : 10.3390/v12060624

Anahtar Kelimeler : SARS-CoV-2, coronavirus, extraction buffer, COVID-19, inactivation, lysis buffer

ISSN: 1999-4915
Cilt: 12
Sayı: 624
Sayfa: 624

Sınıflandırma :

Biyotıp %98

Viroloji %99

7

Phylogenetically based establishment of a dengue virus panel, representing all available genotypes, as a tool in dengue drug discovery

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

Antiviral Research

Yayıncı:

Elsevier

Yazar(lar) :

Franck Touret , Cécile Baronti , Olivia Goethals , Marnix Van Loock , Xavier de Lamballerie , Gilles Querat

Yıl :

2019

Franck Touret

Özet Ek Bilgiler

Kaydet

Dengue fever is the most widespread of the human arbovirus diseases, with approximately one third of the world's population at risk of infection. Dengue viruses are members of the genus Flavivirus (family Flaviviridae) and, antigenically, they separate as four closely related serotypes (1–4) that share 60–75% amino acid homology. This genetic diversity complicates the process of antiviral drug discovery. Thus, currently no approved dengue-specific therapeutic treatments are available. With the aim of providing an efficient tool for dengue virus drug discovery, a collection of nineteen dengue viruses, representing the genotypic diversity within the four serotypes, was developed. After phylogenetic analysis of the full-length genomes, we selected relevant strains from the EVAg collection at Aix-Marseille University and completed the virus collection, using a reverse genetic system based on the infectious sub-genomic amplicons technique. Finally, we evaluated this dengue virus collection against three published dengue inhibitory compounds. NITD008, which targets the highly conserved active site of the viral NS5 polymerase enzyme, exhibited similar antiviral potencies against each of the different dengue genotypes in the panel. Compounds targeting less conserved protein subdomains, such as the capsid inhibitor ST-148, or SDM25N, a ∂ opioid receptor antagonist which indirectly targets NS4B, exhibited larger differences in potency against the various genotypes of dengue viruses. These results illustrate the importance of a phylogenetically based dengue virus reference panel for dengue antiviral research. The collection developed in this study, which includes such representative dengue viruses, has been made available to the scientific community through the European Virus Archive to evaluate novel DENV antiviral candidates.

DOI : 10.1016/j.antiviral.2019.05.005

Anahtar Kelimeler : Dengue virus, Phylogenetic analysis, Reverse genetic, Drug discovery, Virus panel, Dengue inhibitors

ISSN: 0166-3542
Cilt: 168
Sayfa: 109-113

Sınıflandırma :

Yaşam Bilimleri %74

Tıbbi Mikrobiyoloji %71

Biyotıp %26

Viroloji %100

8

In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication

Dergi Makalesi

Kaynak :

Directory of Open Access Journals (DOAJ)

Dergi:

Scientific Reports

Yazar(lar) :

Franck Touret , Magali Gilles , Karine Barral , Antoine Nougairède , Jacques van Helden , Etienne Decroly , Xavier de Lamballerie , Bruno Coutard

Yıl :

2020

Franck Touret

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Abstract A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.

DOI : 10.1038/s41598-020-70143-6

ISSN: 2045-2322
Cilt: 10
Sayı: 1
Sayfa: 1 - 8

9

Dose Rationale for Favipiravir Use in Patients Infected With SARS‐CoV‐2

Dergi Makalesi

Kaynak :

Wiley Online Library

Dergi:

Clinical Pharmacology & Therapeutics

Yazar(lar) :

Philippine Eloy , Caroline Solas , Franck Touret , France Mentré , Denis Malvy , Xavier Lamballerie , Jérémie Guedj

Konu :

Pharmacology (medical), Pharmacology

Yıl :

2020

Franck Touret

Ek Bilgiler

Kaydet

DOI : 10.1002/cpt.1877

ISSN: 0009-9236
Sayı: 2
Cilt: 108
Sayfa: 188-188

10

Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis

Dergi Makalesi

Kaynak :

Springer Nature

Dergi:

Nature Communications

Yayıncı:

Springer Science and Business Media LLC

Yazar(lar) :

Ashleigh Shannon , Barbara Selisko , Nhung-Thi-Tuyet Le , Johanna Huchting , Franck Touret , Géraldine Piorkowski , Véronique Fattorini , François Ferron , Etienne Decroly , Chris Meier , Bruno Coutard , Olve Peersen , Bruno CanardAshleigh Shannon , Barbara Selisko , Nhung-Thi-Tuyet Le , Johanna Huchting , Franck Touret , Géraldine Piorkowski , Véronique Fattorini , François Ferron , Etienne Decroly , Chris Meier , Bruno Coutard , Olve Peersen , Bruno Canard

Yıl :

2020

Franck Touret Franck Touret

Özet Ek Bilgiler

Kaydet

AbstractThe ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.

DOI : 10.1038/s41467-020-18463-z

ISSN: 2041-1723
Sayı: 1
Cilt: 11

11

Drugs against SARS‐CoV ‐2: What do we know about their mode of action?

Dergi Makalesi

Kaynak :

Wiley Online Library

Dergi:

Reviews in Medical Virology

Yazar(lar) :

Coralie Valle , Baptiste Martin , Franck Touret , Ashleigh Shannon , Bruno Canard , Jeanu2010Claude Guillemot , Bruno Coutard , Etienne Decroly

Konu :

Virology, Infectious Diseases

Yıl :

2020

Franck Touret

Özet Ek Bilgiler

Kaydet

The health emergency caused by the recent Covid‐19 pandemic highlights the need to identify effective treatments against the virus causing this disease (SARS‐CoV‐2). The first clinical trials have been testing repurposed drugs that show promising anti‐SARS‐CoV‐2 effects in cultured cells. Although more than 2400 clinical trials are already under way, the actual number of tested compounds is still limited to approximately 20, alone or in combination. In addition, knowledge on their mode of action (MoA) is currently insufficient. Their first results reveal some inconsistencies and contradictory results and suggest that cohort size and quality of the control arm are two key issues for obtaining rigorous and conclusive results. Moreover, the observed discrepancies might also result from differences in the clinical inclusion criteria, including the possibility of early treatment that may be essential for therapy efficacy in patients with Covid‐19. Importantly, efforts should also be made to test new compounds with a documented MoA against SARS‐CoV‐2 in clinical trials. Successful treatment will probably be based on multitherapies with antiviral compounds that target different steps of the virus life cycle. Moreover, a multidisciplinary approach that combines artificial intelligence, compound docking, and robust in vitro and in vivo assays will accelerate the development of new antiviral molecules. Finally, large retrospective studies on hospitalized patients are needed to evaluate the different treatments with robust statistical tools and to identify the best treatment for each Covid‐19 stage. This review describes different candidate antiviral strategies for Covid‐19, by focusing on their mechanism of action.

DOI : 10.1002/rmv.2143

ISSN: 1052-9276
Sayı: 6
Cilt: 30
Sayfa: 1-10

12

Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

Dergi Makalesi

Kaynak :

Springer Nature

Dergi:

Nature Communications

Yayıncı:

Springer Science and Business Media LLC

Yazar(lar) :

Jean-Sélim Driouich , Maxime Cochin , Guillaume Lingas , Grégory Moureau , Franck Touret , Paul-Rémi Petit , Géraldine Piorkowski , Karine Barthélémy , Caroline Laprie , Bruno Coutard , Jérémie Guedj , Xavier de Lamballerie , Caroline Solas , Antoine NougairèdeJean-Sélim Driouich , Maxime Cochin , Guillaume Lingas , Grégory Moureau , Franck Touret , Paul-Rémi Petit , Géraldine Piorkowski , Karine Barthélémy , Caroline Laprie , Bruno Coutard , Jérémie Guedj , Xavier de Lamballerie , Caroline Solas , Antoine Nougairède

Yıl :

2021

Franck Touret Franck Touret

Özet Ek Bilgiler

Kaydet

AbstractDespite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.

DOI : 10.1038/s41467-021-21992-w

ISSN: 2041-1723
Sayı: 1
Cilt: 12

13

Hydroxychloroquine and azithromycin used alone or combined are not effective against SARS-CoV-2 ex vivo and in a hamster model

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

Antiviral Research

Yayıncı:

Elsevier BV

Yazar(lar) :

Maxime Cochin , Franck Touret , Jean-Sélim Driouich , Gregory Moureau , Paul-Rémi Petit , Caroline Laprie , Caroline Solas , Xavier de Lamballerie , Antoine Nougairède

Yıl :

2022

Franck Touret

Özet Ek Bilgiler

Kaydet

Drug repositioning has been used extensively since the beginning of the COVID-19 pandemic in an attempt to identify antiviral molecules for use in human therapeutics. Hydroxychloroquine and azithromycin have shown inhibitory activity against SARS-CoV-2 replication in different cell lines. Based on such in vitro data and despite the weakness of preclinical assessment, many clinical trials were set up using these molecules. In the present study, we show that hydroxychloroquine and azithromycin alone or combined does not block SARS-CoV-2 replication in human bronchial airway epithelia. When tested in a Syrian hamster model, hydroxychloroquine and azithromycin administrated alone or combined displayed no significant effect on viral replication, clinical course of the disease and lung impairments, even at high doses. Hydroxychloroquine quantification in lung tissues confirmed strong exposure to the drug, above in vitro inhibitory concentrations. Overall, this study does not support the use of hydroxychloroquine and azithromycin as antiviral drugs for the treatment of SARS-CoV-2 infections.

DOI : 10.1016/j.antiviral.2021.105212

Anahtar Kelimeler : ACE2 Angiotensin-Converting enzyme 2, Angiotensin-Converting enzyme 2, AZM Azithromycin, Azithromycin, BID Bis in die, Bis in die, COVID-19 Coronavirus disease 2019, Coronavirus disease 2019, CQ Chloroquine, Chloroquine, EC50 50% effective concentrations, 50% effective concentrations, FCS Fetal calf serum, Fetal calf serum, HAE Human airway epithelium, Human airway epithelium, HCQ Hydroxychloroquine, Hydroxychloroquine, H&E Hematoxylin-eosin, Hematoxylin-eosin, IQ Inhibitory quotient, Inhibitory quotient, LDH Lactate dehydrogenase, Lactate dehydrogenase, MERS-CoV Middle East Respiratory Syndrome Coronavirus, Middle East Respiratory Syndrome Coronavirus, MOI Multiplicity of infection, Multiplicity of infection, REM Remdesivir, Remdesivir, RT-qPCR Quantitative real-time RT-PCR, Quantitative real-time RT-PCR, SARS-CoV Severe Acute Respiratory Syndrome Coronavirus, Severe Acute Respiratory Syndrome Coronavirus, SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2, Severe Acute Respiratory Syndrome Coronavirus 2, SD Standard deviation, Standard deviation, TCID50 Median tissue culture infectious dose, Median tissue culture infectious dose, TMPRSS2 Type II transmembrane serine protease, Type II transmembrane serine protease, WHO World Health Organization, World Health Organization, SARS-CoV-2, COVID-19, Coronavirus, Antivirals, Hydroxychloroquine, Azithromycin, In vivo, Syrian hamster, Ex vivo, Human airway epithelium

ISSN: 0166-3542
Cilt: 197
Sayfa: 105212

14

Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients.

Dergi Makalesi

Kaynak :

Directory of Open Access Journals (DOAJ)

Dergi:

PLoS ONE

Yazar(lar) :

Michael C Carlsson , Cecilia Cederfur , Viveka Schaar , Crina I A Balog , Adriana Lepur , Franck Touret , Emma Salomonsson , André M Deelder , Mårten Fernö , Håkan Olsson , Manfred Wuhrer , Hakon Leffler

Yıl :

2011

Franck Touret

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7-2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8-3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20-80) in cancer sera and about 30% (range 25-50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells.

DOI : 10.1371/journal.pone.0026560

ISSN: 1932-6203
Cilt: 6
Sayı: 10
Sayfa: e26560

Sınıflandırma :

Tıp ve Halk Sağlığı %92

Adli Tıp %52

Veterinerlik ve Veterinerlik Bilimi %42

15

Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

Antiviral Research

Yayıncı:

Elsevier BV

Yazar(lar) :

Franck Touret , Jean-Sélim Driouich , Maxime Cochin , Paul Rémi Petit , Magali Gilles , Karine Barthélémy , Grégory Moureau , Francois-Xavier Mahon , Denis Malvy , Caroline Solas , Xavier de Lamballerie , Antoine Nougairède

Yıl :

2021

Franck Touret

Özet Ek Bilgiler

Kaydet

Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has more than twenty years of safe utilization for the treatment of hematological malignancies. In this context, Imatinib was rapidly evaluated in clinical trials against Covid-19. Here, we present the pre-clinical evaluation of imatinib in multiple models. Our results indicated that imatinib and another TKI, the masitinib, exhibit an antiviral activity in VeroE6 cells. However, imatinib was inactive in a reconstructed bronchial human airway epithelium model. In vivo, imatinib therapy failed to impair SARS-CoV-2 replication in a golden Syrian hamster model despite high concentrations in plasma and in the lung. Overall, these results do not support the use of imatinib and similar TKIs as antivirals in the treatment of Covid-19.

DOI : 10.1016/j.antiviral.2021.105137

Anahtar Kelimeler : SARS-CoV-2, Covid-19, Coronavirus, Antivirals, Tyrosine kinase inhibitor, Imatinib

ISSN: 0166-3542
Cilt: 193
Sayfa: 105137

16

A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction

Dergi Makalesi

Kaynak :

Springer Nature

Dergi:

Nature

Yayıncı:

Springer Science and Business Media LLC

Yazar(lar) :

Suzanne J. F. Kaptein , Olivia Goethals , Dominik Kiemel , Arnaud Marchand , Bart Kesteleyn , Jean-François Bonfanti , Dorothée Bardiot , Bart Stoops , Tim H. M. Jonckers , Kai Dallmeier , Peggy Geluykens , Kim Thys , Marjolein Crabbe , Laurent Chatel-Chaix , Max Münster , Gilles Querat , Franck Touret , Xavier de Lamballerie , Pierre Raboisson , Kenny Simmen , Patrick Chaltin , Ralf Bartenschlager , Marnix Van Loock , Johan NeytsSuzanne J. F. Kaptein , Olivia Goethals , Dominik Kiemel , Arnaud Marchand , Bart Kesteleyn , Jean-François Bonfanti , Dorothée Bardiot , Bart Stoops , Tim H. M. Jonckers , Kai Dallmeier , Peggy Geluykens , Kim Thys , Marjolein Crabbe , Laurent Chatel-Chaix , Max Münster , Gilles Querat , Franck Touret , Xavier de Lamballerie , Pierre Raboisson , Kenny Simmen , Patrick Chaltin , Ralf Bartenschlager , Marnix Van Loock , Johan Neyts

Yıl :

2021

Franck Touret Franck Touret

Ek Bilgiler

Kaydet

DOI : 10.1038/s41586-021-03990-6

ISSN: 0028-0836

17

Identification of potent inhibitors of arenavirus and SARS-CoV-2 exoribonucleases by fluorescence polarization assay

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

Antiviral Research

Yayıncı:

Elsevier BV

Yazar(lar) :

Sergio Hernández , Mikael Feracci , Carolina Trajano De Jesus , Priscila El Kazzi , Rafik Kaci , Laura Garlatti , Clemence Mondielli , Fabrice Bailly , Philippe Cotelle , Franck Touret , Xavier de Lamballerie , Bruno Coutard , Etienne Decroly , Bruno Canard , François Ferron , Karine Alvarez

Yıl :

2022

Franck Touret

Özet Ek Bilgiler

Kaydet

Viral exoribonucleases are uncommon in the world of RNA viruses. To date, they have only been identified in the Arenaviridae and the Coronaviridae families. The exoribonucleases of these viruses play a crucial role in the pathogenicity and interplay with host innate immune response. Moreover, coronaviruses exoribonuclease is also involved in a proofreading mechanism ensuring the genetic stability of the viral genome. Because of their key roles in virus life cycle, they constitute attractive target for drug design. Here we developed a sensitive, robust and reliable fluorescence polarization assay to measure the exoribonuclease activity and its inhibition in vitro. The effectiveness of the method was validated on three different viral exoribonucleases, including SARS-CoV-2, Lymphocytic Choriomeningitis and Machupo viruses. We performed a screening of a focused library consisting of 113 metal chelators. Hit compounds were recovered with an IC50 at micromolar level. We confirmed 3 hits in SARS-CoV-2 infected Vero-E6 cells.

DOI : 10.1016/j.antiviral.2022.105364

Anahtar Kelimeler : Phosphohydrolase activity, Arenaviridae, Coronaviridae, Exoribonuclease activity, Fluorescence polarization, Screening, Inhibitors, IC50, Cellular assays

ISSN: 0166-3542
Sayfa: 105364

18

Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates

Dergi Makalesi

Kaynak :

Springer Nature

Dergi:

Nature

Yayıncı:

Springer Nature

Yazar(lar) :

Pauline Maisonnasse , Jérémie Guedj , Vanessa Contreras , Sylvie Behillil , Caroline Solas , Romain Marlin , Thibaut Naninck , Andres Pizzorno , Julien Lemaitre , Antonio Gonçalves , Nidhal Kahlaoui , Olivier Terrier , Raphael Ho Tsong Fang , Vincent Enouf , Nathalie Dereuddre-Bosquet , Angela Brisebarre , Franck Touret , Catherine Chapon , Bruno Hoen , Bruno Lina , Manuel Rosa Calatrava , Sylvie van der Werf , Xavier de Lamballerie , Roger Le Grand

Konu :

Microbiology, Preclinical research, SARS-CoV-2

Yıl :

2020

Franck Touret