Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A90127%2F20%3A00139241" target="_blank" >RIV/00216224:90127/20:00139241 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/20:00531271

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-020-17495-9" target="_blank" >https://www.nature.com/articles/s41467-020-17495-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-020-17495-9" target="_blank" >10.1038/s41467-020-17495-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin

Popis výsledku v původním jazyce

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. 2-O-RNA methyltransferase (MTase) is one of the enzymes of this virus that is a potential target for antiviral therapy as it is crucial for RNA cap formation; an essential process for viral RNA stability. This MTase function is associated with the nsp16 protein, which requires a cofactor, nsp10, for its proper activity. Here we show the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Our structural comparisons reveal low conservation of the MTase catalytic site between Zika and SARS-CoV-2 viruses, but high conservation of the MTase active site between SARS-CoV-2 and SARS-CoV viruses; these data suggest that the preparation of MTase inhibitors targeting several coronaviruses - but not flaviviruses - should be feasible. Together, our data add to important information for structure-based drug discovery. p id=Par SARS-CoV-2 expresses a 2 ' -O RNA methyltransferase (MTase) that is involved in the viral RNA cap formation and therefore a target for antiviral therapy. Here the authors provide the structure of nsp10-nsp16 with the panMTase inhibitor sinefungin and report that the development of MTase inhibitor therapies that target multiple coronoaviruses is feasible.

Název v anglickém jazyce

Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin

Popis výsledku anglicky

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. 2-O-RNA methyltransferase (MTase) is one of the enzymes of this virus that is a potential target for antiviral therapy as it is crucial for RNA cap formation; an essential process for viral RNA stability. This MTase function is associated with the nsp16 protein, which requires a cofactor, nsp10, for its proper activity. Here we show the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Our structural comparisons reveal low conservation of the MTase catalytic site between Zika and SARS-CoV-2 viruses, but high conservation of the MTase active site between SARS-CoV-2 and SARS-CoV viruses; these data suggest that the preparation of MTase inhibitors targeting several coronaviruses - but not flaviviruses - should be feasible. Together, our data add to important information for structure-based drug discovery. p id=Par SARS-CoV-2 expresses a 2 ' -O RNA methyltransferase (MTase) that is involved in the viral RNA cap formation and therefore a target for antiviral therapy. Here the authors provide the structure of nsp10-nsp16 with the panMTase inhibitor sinefungin and report that the development of MTase inhibitor therapies that target multiple coronoaviruses is feasible.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30300 - Health sciences

Projekt

—

Návaznosti

—

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

7

Strana od-do

1-7

Kód UT WoS článku

000556360300010

EID výsledku v databázi Scopus

2-s2.0-85090483661