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Article

CNBP Binds and Unfolds In Vitro G-Quadruplexes Formed in the SARS-CoV-2 Positive and Negative Genome Strands

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Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario (UNR), Ocampo y Esmeralda, Rosario S200EZP, Santa Fe, Argentina
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Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM), Ocampo y Esmeralda, Rosario S200EZP, Santa Fe, Argentina
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Author to whom correspondence should be addressed.
Academic Editor: Vaclav Brazda
Int. J. Mol. Sci. 2021, 22(5), 2614; https://doi.org/10.3390/ijms22052614
Received: 15 January 2021 / Revised: 20 February 2021 / Accepted: 20 February 2021 / Published: 5 March 2021
(This article belongs to the Special Issue Impacts of Molecular Structure on Nucleic Acid–Protein Interactions)
The Coronavirus Disease 2019 (COVID-19) pandemic has become a global health emergency with no effective medical treatment and with incipient vaccines. It is caused by a new positive-sense RNA virus called severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). G-quadruplexes (G4s) are nucleic acid secondary structures involved in the control of a variety of biological processes including viral replication. Using several G4 prediction tools, we identified highly putative G4 sequences (PQSs) within the positive-sense (+gRNA) and negative-sense (−gRNA) RNA strands of SARS-CoV-2 conserved in related betacoronaviruses. By using multiple biophysical techniques, we confirmed the formation of two G4s in the +gRNA and provide the first evidence of G4 formation by two PQSs in the −gRNA of SARS-CoV-2. Finally, biophysical and molecular approaches were used to demonstrate for the first time that CNBP, the main human cellular protein bound to SARS-CoV-2 RNA genome, binds and promotes the unfolding of G4s formed by both strands of SARS-CoV-2 RNA genome. Our results suggest that G4s found in SARS-CoV-2 RNA genome and its negative-sense replicative intermediates, as well as the cellular proteins that interact with them, are relevant factors for viral genes expression and replication cycle, and may constitute interesting targets for antiviral drugs development. View Full-Text
Keywords: COVID-19; SARS-CoV-2; coronavirus; G-quadruplex; CNBP COVID-19; SARS-CoV-2; coronavirus; G-quadruplex; CNBP
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MDPI and ACS Style

Bezzi, G.; Piga, E.J.; Binolfi, A.; Armas, P. CNBP Binds and Unfolds In Vitro G-Quadruplexes Formed in the SARS-CoV-2 Positive and Negative Genome Strands. Int. J. Mol. Sci. 2021, 22, 2614. https://doi.org/10.3390/ijms22052614

AMA Style

Bezzi G, Piga EJ, Binolfi A, Armas P. CNBP Binds and Unfolds In Vitro G-Quadruplexes Formed in the SARS-CoV-2 Positive and Negative Genome Strands. International Journal of Molecular Sciences. 2021; 22(5):2614. https://doi.org/10.3390/ijms22052614

Chicago/Turabian Style

Bezzi, Georgina, Ernesto J. Piga, Andrés Binolfi, and Pablo Armas. 2021. "CNBP Binds and Unfolds In Vitro G-Quadruplexes Formed in the SARS-CoV-2 Positive and Negative Genome Strands" International Journal of Molecular Sciences 22, no. 5: 2614. https://doi.org/10.3390/ijms22052614

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