Discovery of G-quadruplex-forming sequences in SARS-CoV-2.
Brief Bioinform
; 22(2): 1150-1160, 2021 03 22.
Article
in English
| MEDLINE | ID: covidwho-1352102
ABSTRACT
The outbreak caused by the novel coronavirus SARS-CoV-2 has been declared a global health emergency. G-quadruplex structures in genomes have long been considered essential for regulating a number of biological processes in a plethora of organisms. We have analyzed and identified 25 four contiguous GG runs (G2NxG2NyG2NzG2) in the SARS-CoV-2 RNA genome, suggesting putative G-quadruplex-forming sequences (PQSs). Detailed analysis of SARS-CoV-2 PQSs revealed their locations in the open reading frames of ORF1 ab, spike (S), ORF3a, membrane (M) and nucleocapsid (N) genes. Identical PQSs were also found in the other members of the Coronaviridae family. The top-ranked PQSs at positions 13385 and 24268 were confirmed to form RNA G-quadruplex structures in vitro by multiple spectroscopic assays. Furthermore, their direct interactions with viral helicase (nsp13) were determined by microscale thermophoresis. Molecular docking model suggests that nsp13 distorts the G-quadruplex structure by allowing the guanine bases to be flipped away from the guanine quartet planes. Targeting viral helicase and G-quadruplex structure represents an attractive approach for potentially inhibiting the SARS-CoV-2 virus.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
G-Quadruplexes
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Brief Bioinform
Journal subject:
Biology
/
Medical Informatics
Year:
2021
Document Type:
Article
Affiliation country:
Bib
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