Discovery of G-quadruplex-forming sequences in SARS-CoV-2
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AbstractThe 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.
Acceptance Date12/05/2020
All Author(s) ListJi D, Juhas M, Tsang CM, Kwok CK, Li Y, Zhang Y
Journal nameBriefings in Bioinformatics
Year2021
Month3
Volume Number22
Issue Number2
PublisherOxford University Press
Pages1150 - 1160
ISSN1467-5463
eISSN1477-4054
LanguagesEnglish-United Kingdom

Last updated on 2021-27-07 at 23:53