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

J 2020

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

KRAFCIKOVA, Petra; Jan SILHAN; Radim NENCKA a Evzen BOURA

Základní údaje

Originální název

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

Autoři

KRAFCIKOVA, Petra; Jan SILHAN; Radim NENCKA a Evzen BOURA

Vydání

Nature Communications, London, Nature Publishing Group, 2020, 2041-1723

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30300 3.3 Health sciences

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 14.919

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:90127/20:00139241

Organizační jednotka

CIISB II

Klíčová slova anglicky

CRYSTAL-STRUCTURE; CORONAVIRUS; VIRUS; DISCOVERY; METHYLATION

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 9. 2025 12:00, Mgr. Petra Trembecká, Ph.D.

Anotace

V originále

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.

Návaznosti

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

KRAFCIKOVA, Petra; Jan SILHAN; Radim NENCKA a Evzen BOURA. Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin. Nature Communications. London: Nature Publishing Group, 2020, roč. 11, č. 1, s. 1-7. ISSN 2041-1723. Dostupné z: https://doi.org/10.1038/s41467-020-17495-9.

@article{2487423,
   author = {Krafcikova, Petra and Silhan, Jan and Nencka, Radim and Boura, Evzen},
   article_location = {London},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41467-020-17495-9},
   keywords = {CRYSTAL-STRUCTURE; CORONAVIRUS; VIRUS; DISCOVERY; METHYLATION},
   language = {eng},
   issn = {2041-1723},
   journal = {Nature Communications},
   title = {Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin},
   url = {https://www.nature.com/articles/s41467-020-17495-9},
   volume = {11},
   year = {2020}
}

TY  - JOUR
ID  - 2487423
AU  - Krafcikova, Petra - Silhan, Jan - Nencka, Radim - Boura, Evzen
PY  - 2020
TI  - Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin
JF  - Nature Communications
VL  - 11
IS  - 1
SP  - 1-7
EP  - 1-7
PB  - Nature Publishing Group
SN  - 20411723
KW  - CRYSTAL-STRUCTURE
KW  - CORONAVIRUS
KW  - VIRUS
KW  - DISCOVERY
KW  - METHYLATION
UR  - https://www.nature.com/articles/s41467-020-17495-9
N2  - 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.
ER  -

KRAFCIKOVA, Petra; Jan SILHAN; Radim NENCKA a Evzen BOURA. Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin. \textit{Nature Communications}. London: Nature Publishing Group, 2020, roč.~11, č.~1, s.~1-7. ISSN~2041-1723. Dostupné z: https://doi.org/10.1038/s41467-020-17495-9.

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