Abstract
The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is one of seven human coronaviruses. G-quadruplexes are intrinsic obstacles to genome replication. Whether G-quadruplexes are present in human coronaviruses is unknown. In the current study, we have predicted that all seven human coronaviruses harbor G-quadruplex sequences. Conserved G-quadruplex sequences in SARS-CoV and SARS-CoV-2 were analyzed and verified by circular dichroism (CD) spectroscopy and Thioflavin T fluorescence assay. Similar to SARS-CoV, SARS-CoV-2 encodes an nsP3 protein, which is predicted to associate with G-quadruplexes. Targeting G-quadruplex sequences in the SARS-CoV-2 genome by G-quadruplex ligands could be a new way to conquer COVID-19.
Highlights
Ongoing coronavirus disease 2019 (COVID-19) pandemic has been a major global threat for human health (Lu and Zhang, 2020; Tu et al, 2020), with over 20 million confirmed cases in over 200 countries and regions
Genomes of bat SARSr-CoV as well as SARS-CoV and SARS-CoV-2 strains were downloaded from the NCBI virus database
Our study provides a paradigm for assessing G4 functions in viral genomes
Summary
Ongoing coronavirus disease 2019 (COVID-19) pandemic has been a major global threat for human health (Lu and Zhang, 2020; Tu et al, 2020), with over 20 million confirmed cases in over 200 countries and regions. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus genus of Coronaviridae family. Among seven types of Coronaviridae family of viruses which could infect humans, HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 are common around the world, but SARS-CoV, MERS-CoV, and SARS-CoV-2 are more recent and rare. Both SARS-CoV-2 and SARS-CoV are human SARS-related coronavirus (SARSr-CoVs). One of the most complex tasks for all viruses is to replicate the entire genome. There are intrinsic obstacles to genome replication. The folding of G-rich sequences into G-quadruplex structures is one source of replication stress. G-tetrads are formed around K+ ions through four Hoogsteen-type hydrogen bonds, and the tetrads stack to adopt G4 structures (Figure 1A)
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