{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:13:36Z","timestamp":1771244016245,"version":"3.50.1"},"reference-count":93,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Foundation of Ukraine","award":["Project #2021.01\/0087"],"award-info":[{"award-number":["Project #2021.01\/0087"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>G-quadruplexes (G4s) are emerging as potential antiviral targets. SARS-CoV-2 genomic RNA contains 42 G-rich regions harboring putative G-quadruplex-forming sequences (PQSs). Here, we performed a systematic genomic and structural analysis of SARS-CoV-2 PQSs. It was proposed that non-G-tetrads or different triads may stabilize most G4s in this RNA. Many G4s may include the most stable U\u00b7A-U triad. Several G-quadruplexes may be significantly stabilized by 3\u2032 U-tetrad. Large-scale mutational analysis of RNA structural elements containing PQSs showed that most PQSs are highly conserved, while persistent G4-destroying mutations were observed only for one PQS and were transient for two others. Based on G4 position and structural context, we propose that: (i) G4 370 in nsp1 may contribute to cap-independent translation initiation; (ii) certain putative G4s in different genes may assist in co-translational folding of viral proteins; (iii) G4 13385, located upstream of the frameshift stimulation element, may promote formation of a pseudoknot competent for \u22121 frameshifting. For putative G4s at positions 3467, 13385 and 28903, we analyzed binding to 13 compounds by molecular docking and selected four candidates for molecular dynamics simulations. The ligand EKM emerged as a promising antiviral candidate due to its specific binding to G4 3467.<\/jats:p>","DOI":"10.3390\/v18020253","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:11:28Z","timestamp":1771240288000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Search of the Most Significant Potential G-Quadruplexes in SARS-CoV-2 RNA: Genomic Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Margarita","family":"Zarudnaya","sequence":"first","affiliation":[{"name":"Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-9218","authenticated-orcid":false,"given":"Ivan","family":"Voiteshenko","sequence":"additional","affiliation":[{"name":"Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., 03143 Kyiv, Ukraine"},{"name":"Educational and Scientific Institute of High Technologies, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Street, 01033 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasyl","family":"Hurmah","sequence":"additional","affiliation":[{"name":"Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetiana","family":"Shyryna","sequence":"additional","affiliation":[{"name":"Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1664-6837","authenticated-orcid":false,"given":"Alex","family":"Nyporko","sequence":"additional","affiliation":[{"name":"Educational and Scientific Institute of High Technologies, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Street, 01033 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maksym","family":"Platonov","sequence":"additional","affiliation":[{"name":"Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szczepan","family":"Roszak","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroc\u0142aw, 50370 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7845-4884","authenticated-orcid":false,"given":"Bakhtiyor","family":"Rasulev","sequence":"additional","affiliation":[{"name":"Department of Coatings and Polymeric Materials, North Dakota State University, NDSU Department 2510, P.O. Box 6050, Fargo, ND 58108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-4098","authenticated-orcid":false,"given":"Karina","family":"Kapusta","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Physics, Tougaloo College, Tougaloo, MS 39174, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7932-9105","authenticated-orcid":false,"given":"Leonid","family":"Gorb","sequence":"additional","affiliation":[{"name":"Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1016\/j.jmb.2017.05.017","article-title":"RNA G-Quadruplexes in Biology: Principles and Molecular Mechanisms","volume":"429","author":"Fay","year":"2017","journal-title":"J. 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