Anti-HCV and Zika activities of ribavirin C-nucleosides analogues

González, Sergio; Brzuska, Gabriela; Ouarti, Abdelhakim; Gallier, Florian; Solarte, Carmen; Ferry, Angélique; Uziel, Jacques; Król, Ewelina; Lubin‐Germain, Nadège

doi:10.1016/j.bmc.2022.116858

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…We validated the application of the rGI-Gluc in an antiviral drug screening assay using three compounds, ARDP0006, 27-hydroxycholesterol, and ribavirin, which exhibit antiviral activity against other viruses [ 29 , 30 , 31 ]. ARDP0006 and ribavirin possessed a potent inhibitory effect on virus propagation based on the reduction in the luciferase activity, whereas no obvious inhibition effect of 27-hydroxycholesterol on the JEV was observed ( Figure 3 E).…”

Section: Resultsmentioning

confidence: 99%

A Recombinant Genotype I Japanese Encephalitis Virus Expressing a Gaussia Luciferase Gene for Antiviral Drug Screening Assay and Neutralizing Antibodies Detection

Chen

et al. 2022

IJMS

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Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in humans throughout Asia. In the past twenty years, the emergence of the genotype I (GI) JEV as the dominant genotype in Asian countries has raised a significant threat to public health security. However, no clinically approved drug is available for the specific treatment of JEV infection, and the commercial vaccines derived from the genotype III JEV strains merely provided partial protection against the GI JEV. Thus, an easy-to-perform platform in high-throughput is urgently needed for the antiviral drug screening and assessment of neutralizing antibodies specific against the GI JEV. In this study, we established a reverse genetics system for the GI JEV strain (YZ-1) using a homologous recombination strategy. Using this reverse genetic system, a gaussia luciferase (Gluc) expression cassette was inserted into the JEV genome to generate a reporter virus (rGI-Gluc). The reporter virus exhibited similar growth kinetics to the parental virus and remained genetically stable for at least ten passages in vitro. Of note, the bioluminescence signal strength of Gluc in the culture supernatants was well correlated with the viral progenies determined by viral titration. Taking advantage of this reporter virus, we established Gluc readout-based assays for antiviral drug screening and neutralizing antibody detection against the GI JEV. These Gluc readout-based assays exhibited comparable performance to the assays using an actual virus and are less time consuming and are applicable for a high-throughput format. Taken together, we generated a GI JEV reporter virus expressing a Gluc gene that could be a valuable tool for an antiviral drug screening assay and neutralization assay.

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Section: Resultsmentioning

confidence: 99%

A Recombinant Genotype I Japanese Encephalitis Virus Expressing a Gaussia Luciferase Gene for Antiviral Drug Screening Assay and Neutralizing Antibodies Detection

Chen

et al. 2022

IJMS

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“…Nevertheless, trends can be found in a few studies regarding antiviral and antitumor activities. recently, [68] the compounds 48a, 48c, and 48e showed moderate antiviral activities (µM range) (Table 1). The highest activity was observed for compounds 48a and 48e (60% and 67% inhibition of hepatitis C virus cell culture replication, respectively).…”

Section: Biological Activitymentioning

confidence: 92%

Developments in the chemistry and biology of 1,2,3‐triazolyl‐C‐nucleosides

Nascimento,

Ferry,

Gallier

et al. 2023

Archiv der Pharmazie

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In the last 50 years, nucleoside analogs have been introduced to drug therapy as antivirals for different types of cancer due to their interference in cellular proliferation. Among the first line of nucleoside treatment drugs, ribavirin (RBV) is a synthetic N‐nucleoside with a 1,2,4‐triazole moiety that acts as a broad‐spectrum antiviral. It is on the World Health Organization (WHO) list of essential medicines. However, this important drug therapy causes several side effects due to its nonspecific mechanism of action. There is thus a need for a continuous study of its scaffold. A particular approach consists of connecting d‐ribose to the nitrogen‐containing base with a C–C bond. It provides more stability against enzymatic action and a better pharmacologic profile. The coronavirus disease (COVID) pandemic has increased the need for more solutions for the treatment of viral infections. Among these solutions, remdesivir, the first C‐nucleoside, has been approved by the Food and Drug Administration (FDA) for clinical use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It drew attention to the study of the C‐nucleoside scaffold. Different C‐nucleoside patterns have been synthesized over the years. They show many important activities against viruses and cancer cell lines. 1,2,3‐Triazolyl‐C‐nucleoside derivatives are a prolific and efficient subclass of RBV analogs close to the already‐known RBV with a C–C bond modification. These compounds are often prepared by alkynylation of the d‐ribose ring followed by azide‐alkyne cycloaddition. They are reported to be active against the Crimean‐Congo hemorrhagic fever virus and several tumoral cell lines, showing promising biological potential. In this review, we explore such approaches to 1,2,3‐triazolyl‐C‐nucleosides and their evolution over the years.

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“…For example, the antimalarial drug chloroquine has been shown to limit viral entry, with in vitro EC 50 values 2 of 15 of about 5 µM, but it is barely active in animal models [6,7]. Among the nucleoside analogs, the broad-spectrum antiviral ribavirin is only moderately active against ZIKV, with EC 50 values in the high micromolar range [8]. Inhibitors targeting the helicases NS3 and the bifunctional NS5 protein, such as suramin, sofosbuvir, and sinefungin, also appear to be promising in in vitro assays [9,10].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Non-Nucleoside Inhibitors of Zika Virus NS5 Protein Targeting MTase Activity

Fiorucci,

Meaccini,

Poli

et al. 2024

IJMS

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Zika virus (ZIKV) is a positive-sense single-stranded virus member of the Flaviviridae family. Among other arboviruses, ZIKV can cause neurological disorders such as Guillain Barré syndrome, and it can have congenital neurological manifestations and affect fertility. ZIKV nonstructural protein 5 (NS5) is essential for viral replication and limiting host immune detection. Herein, we performed virtual screening to identify novel small-molecule inhibitors of the ZIKV NS5 methyltransferase (MTase) domain. Compounds were tested against the MTases of both ZIKV and DENV, demonstrating good inhibitory activities against ZIKV MTase. Extensive molecular dynamic studies conducted on the series led us to identify other derivatives with improved activity against the MTase and limiting ZIKV infection with an increased selectivity index. Preliminary pharmacokinetic parameters have been determined, revealing excellent stability over time. Preliminary in vivo toxicity studies demonstrated that the hit compound 17 is well tolerated after acute administration. Our results provide the basis for further optimization studies on novel non-nucleoside MTase inhibitors.

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Anti-HCV and Zika activities of ribavirin C-nucleosides analogues

Cited by 5 publications

References 33 publications

A Recombinant Genotype I Japanese Encephalitis Virus Expressing a Gaussia Luciferase Gene for Antiviral Drug Screening Assay and Neutralizing Antibodies Detection

A Recombinant Genotype I Japanese Encephalitis Virus Expressing a Gaussia Luciferase Gene for Antiviral Drug Screening Assay and Neutralizing Antibodies Detection

Developments in the chemistry and biology of 1,2,3‐triazolyl‐C‐nucleosides

Identification of Novel Non-Nucleoside Inhibitors of Zika Virus NS5 Protein Targeting MTase Activity

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