Inhibitors of mpox VP39 2′-O methyltransferase efficiently inhibit the monkeypox virus

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00576080" target="_blank" >RIV/61388963:_____/23:00576080 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.antiviral.2023.105714" target="_blank" >https://doi.org/10.1016/j.antiviral.2023.105714</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.antiviral.2023.105714" target="_blank" >10.1016/j.antiviral.2023.105714</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Inhibitors of mpox VP39 2′-O methyltransferase efficiently inhibit the monkeypox virus

Popis výsledku v původním jazyce

The RNA 2′-O methyltransferase (MTase) VP39 of the monkeypox virus (MpxV) participates in RNA capping within poxviruses. Sub-micromolar inhibitors targeting this enzyme were already reported. However, these 7-deaza analogs of S-adenosyl methionine (SAH) had not been tested in cellular assays until now. In this study, we employed plaque assays and cytopathic effect-based assays to evaluate the effectiveness of these compounds. All tested compounds demonstrated antiviral activity against MpxV, with EC50 values ranging from 0.06 to 2.7 μM. Nevertheless, some of these compounds also exhibited cytotoxicity in HeLa cells, while others showed no toxicity. Notably, the non-toxic compounds featured a large aromatic substituent at the 7-deaza position, whereas the toxic compounds had a small substituent at the same position. These findings suggest that VP39 represents a bona fide target for the development of antiviral drugs against MpxV.

Název v anglickém jazyce

Inhibitors of mpox VP39 2′-O methyltransferase efficiently inhibit the monkeypox virus

Popis výsledku anglicky

The RNA 2′-O methyltransferase (MTase) VP39 of the monkeypox virus (MpxV) participates in RNA capping within poxviruses. Sub-micromolar inhibitors targeting this enzyme were already reported. However, these 7-deaza analogs of S-adenosyl methionine (SAH) had not been tested in cellular assays until now. In this study, we employed plaque assays and cytopathic effect-based assays to evaluate the effectiveness of these compounds. All tested compounds demonstrated antiviral activity against MpxV, with EC50 values ranging from 0.06 to 2.7 μM. Nevertheless, some of these compounds also exhibited cytotoxicity in HeLa cells, while others showed no toxicity. Notably, the non-toxic compounds featured a large aromatic substituent at the 7-deaza position, whereas the toxic compounds had a small substituent at the same position. These findings suggest that VP39 represents a bona fide target for the development of antiviral drugs against MpxV.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Antiviral Research

ISSN

0166-3542

e-ISSN

1872-9096

Svazek periodika

218

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

3

Strana od-do

105714

Kód UT WoS článku

001082219800001

EID výsledku v databázi Scopus

2-s2.0-85171358493