SARS-CoV‑2 RNA's Dual Identity: G‑Quadruplex versus Hairpin

Alex Nyporko; Ivan Voiteshenko; Margarita Zarudnaya; Vasyl Hurmach; Tetiana Shyryna; Maksym Platonov; Szczepan Roszak; Bakhtiyor Rasulev; Leonid Gorb

doi:10.1021/acsomega.5c02568

SARS-CoV‑2 RNA's Dual Identity: G‑Quadruplex versus Hairpin

ACS Omega. 2025 Jul 1;10(27):29408-29420. doi: 10.1021/acsomega.5c02568. eCollection 2025 Jul 15.

Authors

Alex Nyporko¹, Ivan Voiteshenko^{1

2}, Margarita Zarudnaya², Vasyl Hurmach², Tetiana Shyryna², Maksym Platonov², Szczepan Roszak³, Bakhtiyor Rasulev⁴, Leonid Gorb²

Affiliations

¹ Taras Shevchenko National University of Kyiv, 60 Volodymyrska Street, Kyiv 01033, Ukraine.
² Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., Kyiv 03143, Ukraine.
³ Faculty of Chemistry, University of Wrocław, Wrocław 50370, Poland.
⁴ Department of Coatings and Polymeric Materials, North Dakota State University, ND SU Dept. 2510, PO Box 6050, Fargo, North Dakota 58108, United States.

Abstract

Regardless of advances in biophysical assays for studying G-quadruplexes formation, their high-resolution structural characterization remains limited. In this computational study, the 2D and 3D geometry, energetics, and dynamics of the SARS-CoV-2 potential quadruplex at position 28903 were studied. Two- and three-dimensional structures for four G4-Quadruplexes and three hairpins were predicted using bioinformatics tools. The dynamics, relative stability, impact, and presence of a pseudouridine site were examined in detail. It was hypothesized that the dynamic stability of G4-quadruplexes critically depends on the number of Hoogsteen connections, which stabilize the G4-quadruplex structure. It was also shown that the presence of pseudouridine colocalized with potential quadruplex at position 28903 could enhance the dynamic stability of hairpins and destabilize the structure of G4-quadruplex up to direct unwinding.