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Cytidine nucleoside analog is an effective antiviral drug against Trichomonasvirus

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F22%3A10444302" target="_blank" >RIV/00216208:11310/22:10444302 - isvavai.cz</a>

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ZU6ZQmnYI9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ZU6ZQmnYI9</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.jmii.2021.08.008" target="_blank" >10.1016/j.jmii.2021.08.008</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Cytidine nucleoside analog is an effective antiviral drug against Trichomonasvirus

  • Original language description

    Background: Trichomonas vaginalis is the causative agent of a sexually transmitted disease in humans. The virulence of the parasite depends on multiple factors, including the presence of endosymbiotic dsRNA viruses. The presence of Trichomonasviruses (TVV) was associated with more severe genital symptoms, increased proinflammatory host reactions, and modulated parasite sensitivity to metronidazole. However, no efficient antiviral drugs are available against TVV to derive isogenic TVV-positive and TVV-negative cell lines that are essential for investigations of the TVV impact on T. vaginalis biology.Methods: 7-Deaza-20-C-methyladenosine (7d2CMA) and 20-C-methylcytidine (2CMC) were used for TVV inhibitory assay. TVV replication was monitored using quantitative reverse transcription PCR (RT qPCR) and western blotting. Modeling of TVV1 RNA-dependent RNA polymerase (RdRp) was performed to visualize the inhibitor-RdRp interaction. Susceptibility to metronidazole was performed under aerobic and anaerobic conditions.Results: We demonstrated that 2CMC but not 7d2CMA is a potent inhibitor of TVV replication. Molecular modeling suggested that the RdRp active site can accommodate 2CMC in the active triphosphate nucleotide form. The effect of 2CMC was shown on strains infected with a single and multiple TVV species. The optimal 2CMC concentration (10mM) demonstrated strong selectivity for TVVs over trichomonad growth. The presence of TVV has no effect on T. vaginalis metronidazole susceptibility in derived isogenic cell lines.Conclusions: 2CMC acts against TVVs and represents a new inhibitor against Totiviridae viruses. Our isogenic clones are now available for further studies of various aspects of T. vaginalis biology related to TVV infection. Copyright (c) 2021, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10600 - Biological sciences

Result continuities

  • Project

    <a href="/en/project/GC19-18773J" target="_blank" >GC19-18773J: Modulation of exosomal cargo by T. vaginalis endosymbionts</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Microbiology, Immunology and Infection

  • ISSN

    1684-1182

  • e-ISSN

    1995-9133

  • Volume of the periodical

    55

  • Issue of the periodical within the volume

    2

  • Country of publishing house

    TW - TAIWAN (PROVINCE OF CHINA)

  • Number of pages

    8

  • Pages from-to

    191-198

  • UT code for WoS article

    000796189400006

  • EID of the result in the Scopus database

    2-s2.0-85114114433