{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T21:33:12Z","timestamp":1774301592635,"version":"3.50.1"},"reference-count":62,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,1,29]],"date-time":"2027-01-29T00:00:00Z","timestamp":1801180800000},"content-version":"am","delay-in-days":699,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Telethon Foundation","doi-asserted-by":"publisher","award":["GGP20039"],"award-info":[{"award-number":["GGP20039"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["COC-1-2023-CNR"],"award-info":[{"award-number":["COC-1-2023-CNR"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["2022443ZCW"],"award-info":[{"award-number":["2022443ZCW"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006433","name":"Barcelona Supercomputing Center","doi-asserted-by":"publisher","award":["QH-2024-3-0002"],"award-info":[{"award-number":["QH-2024-3-0002"]}],"id":[{"id":"10.13039\/501100006433","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012032","name":"Romeo and Enrica Invernizzi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1016\/j.ejmech.2025.117302","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T03:29:16Z","timestamp":1737430156000},"page":"117302","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["The chiral 5,6-cyclohexane-fused uracil ring-system: A molecular platform with promising activity against SARS-CoV-2"],"prefix":"10.1016","volume":"286","author":[{"given":"Enrico","family":"Marcantonio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora","family":"Guazzetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crescenzo","family":"Coppa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Battistini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Sartori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Bugatti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Becky","family":"Provinciael","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Curti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Contini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Vermeire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-781X","authenticated-orcid":false,"given":"Franca","family":"Zanardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.117302_bib1","doi-asserted-by":"crossref","first-page":"9128","DOI":"10.1002\/anie.201404761","article-title":"Advancing the drug discovery and development process","volume":"53","author":"Nicolaou","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2025.117302_bib2","doi-asserted-by":"crossref","DOI":"10.1126\/science.aat0805","article-title":"The importance of synthetic chemistry in the pharmaceutical industry","volume":"363","author":"Campos","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2025.117302_bib3","doi-asserted-by":"crossref","first-page":"10150","DOI":"10.1021\/acs.jmedchem.3c00501","article-title":"Synthetic approaches to the new drugs approved during 2021","volume":"66","author":"McInturff","year":"2023","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib4","unstructured":"H. Ritchie, et al. Coronavirus Pandemic (COVID-19). https:\/\/ourworldindata.org\/coronavirus, access date."},{"key":"10.1016\/j.ejmech.2025.117302_bib5","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12985-021-01526-y","article-title":"Precision therapeutic targets for COVID-19","volume":"18","author":"Krumm","year":"2021","journal-title":"Virol. J."},{"key":"10.1016\/j.ejmech.2025.117302_bib6","doi-asserted-by":"crossref","first-page":"9789","DOI":"10.1002\/anie.202008835","article-title":"Molecular insights into small\u2010molecule drug discovery for SARS\u2010CoV\u20102","volume":"60","author":"Su","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2025.117302_bib7","article-title":"Mechanism of action of small-molecule agents in ongoing clinical trials for SARS-CoV-2: a review","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.117302_bib8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2025.117302_bib9","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1021\/acs.jmedchem.2c00117","article-title":"Discovery of S-217622, a noncovalent oral SARS-CoV-2 3CL protease inhibitor clinical candidate for treating COVID-19","volume":"65","author":"Unoh","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib10","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1021\/acscentsci.2c01359","article-title":"Development of highly potent noncovalent inhibitors of SARS-CoV-2 3CLpro","volume":"9","author":"Hou","year":"2023","journal-title":"ACS Cent. Sci."},{"key":"10.1016\/j.ejmech.2025.117302_bib11","doi-asserted-by":"crossref","first-page":"7561","DOI":"10.1021\/acs.jmedchem.2c00303","article-title":"Progress and challenges in targeting the SARS-CoV-2 papain-like protease","volume":"65","author":"Tan","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib12","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1021\/acs.jmedchem.0c01140","article-title":"Targeting SARS-CoV-2 proteases and polymerase for COVID-19 treatment: state of the art and future opportunities","volume":"65","author":"Cannalire","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib13","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1146\/annurev-pharmtox-061220-093932","article-title":"Structural basis of SARS-CoV-2\u2013 and SARS-CoV\u2013receptor binding and small-molecule blockers as potential therapeutics","volume":"61","author":"Sivaraman","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.ejmech.2025.117302_bib14","unstructured":"https:\/\/www.cdc.gov\/covid\/treatment\/?CDC_AAref_Val=https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/your-health\/treatments-for-severe-illness.html, access date."},{"key":"10.1016\/j.ejmech.2025.117302_bib15","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa2118542","article-title":"Oral nirmatrelvir for high-risk, nonhospitalized adults with covid-19","volume":"386","author":"Hammond","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2025.117302_bib16","first-page":"1084","article-title":"Mechanism of reaction of RNA-dependent RNA polymerase from SARS-CoV-2","volume":"2","author":"Aranda","year":"2022","journal-title":"Chem Catal."},{"key":"10.1016\/j.ejmech.2025.117302_bib17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-021-00432-z","article-title":"Structures and functions of coronavirus replication\u2013transcription complexes and their relevance for SARS-CoV-2 drug design","volume":"23","author":"Malone","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ejmech.2025.117302_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115292","article-title":"Potential RNA-dependent RNA polymerase (RdRp) inhibitors as prospective drug candidates for SARS-CoV-2","volume":"252","author":"Bekheit","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s41061-023-00432-x","article-title":"Structure-based drug design of RdRp inhibitors against SARS-CoV-2","volume":"381","author":"Shehzadi","year":"2023","journal-title":"Top. Curr. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2022.115279","article-title":"An update on inhibitors targeting RNA-dependent RNA polymerase for COVID-19 treatment: promises and challenges","volume":"205","author":"Xu","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.117302_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113201","article-title":"RNA-dependent RNA polymerase (RdRp) inhibitors: the current landscape and repurposing for the COVID-19 pandemic","volume":"213","author":"Tian","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib22","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1126\/science.abc1560","article-title":"Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir","volume":"368","author":"Yin","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2025.117302_bib23","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41594-021-00570-0","article-title":"Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin","volume":"28","author":"Yin","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ejmech.2025.117302_bib24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrd3410","article-title":"The resurgence of covalent drugs","volume":"10","author":"Singh","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2025.117302_bib25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4155\/fmc-2020-0236","article-title":"10 years into the resurgence of covalent drugs","volume":"13","author":"De Vita","year":"2021","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib26","doi-asserted-by":"crossref","first-page":"8699","DOI":"10.1021\/acs.jmedchem.2c00473","article-title":"Rings in clinical trials and drugs: present and future","volume":"65","author":"Shearer","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib27","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1021\/jm901241e","article-title":"Escape from flatland: increasing saturation as an approach to improving clinical success","volume":"52","author":"Lovering","year":"2009","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116180","article-title":"Recent advancements in the discovery of small-molecule non-nucleoside inhibitors targeting SARS-CoV-2 RdRp","volume":"171","author":"Zhou","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2025.117302_bib29","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-14664-2","article-title":"Quercetin and luteolin are single-digit micromolar inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase","volume":"12","author":"Munaf\u00f2","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2025.117302_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2020.153440","article-title":"Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections","volume":"86","author":"Jin","year":"2021","journal-title":"Phytomedicine"},{"key":"10.1016\/j.ejmech.2025.117302_bib31","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1080\/22221751.2020.1772676","article-title":"Gemcitabine, lycorine and oxysophoridine inhibit novel coronavirus (SARS-CoV-2) in cell culture","volume":"9","author":"Zhang","year":"2020","journal-title":"Emerg. Microb. Infect."},{"key":"10.1016\/j.ejmech.2025.117302_bib32","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.apsb.2021.02.011","article-title":"Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase","volume":"11","author":"Li","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.ejmech.2025.117302_bib33","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1002\/ptr.7486","article-title":"Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS-CoV-2","volume":"36","author":"Hamdy","year":"2022","journal-title":"Phytother Res."},{"key":"10.1016\/j.ejmech.2025.117302_bib34","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3390\/microorganisms9050893","article-title":"Baicalein and baicalin inhibit SARS-CoV-2 RNA-dependent-RNA polymerase","volume":"9","author":"Zandi","year":"2021","journal-title":"Microorganisms"},{"key":"10.1016\/j.ejmech.2025.117302_bib35","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.3390\/biomedicines10051170","article-title":"Natural polyphenols, 1,2,3,4,6-O-pentagalloyglucose and proanthocyanidins, as broad-spectrum anticoronaviral inhibitors targeting Mpro and RdRp of SARS-CoV-2","volume":"10","author":"Jin","year":"2022","journal-title":"Biomedicines"},{"key":"10.1016\/j.ejmech.2025.117302_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2021.105209","article-title":"2-((1H-indol-3-yl)thio)-N-phenyl-acetamides: SARS-CoV-2 RNA-dependent RNA polymerase inhibitors","volume":"196","author":"Zhao","year":"2021","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2025.117302_bib37","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1021\/acsinfecdis.1c00083","article-title":"Quinoline and quinazoline derivatives inhibit viral RNA synthesis by SARS-CoV-2 RdRp","volume":"7","author":"Zhao","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.ejmech.2025.117302_bib38","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.3390\/v13081585","article-title":"Non-nucleotide RNA-dependent RNA polymerase inhibitor that blocks SARS-CoV-2 replication","volume":"13","author":"Dejmek","year":"2021","journal-title":"Viruses"},{"key":"10.1016\/j.ejmech.2025.117302_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2023.117179","article-title":"Design, synthesis, docking, and biochemical characterization of non-nucleoside SARS-CoV-2 RdRp inhibitors","volume":"80","author":"Brindani","year":"2023","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib40","doi-asserted-by":"crossref","first-page":"7732","DOI":"10.3390\/molecules27227732","article-title":"Structural homology-based drug repurposing approach for targeting NSP12 SARS-CoV-2","volume":"27","author":"Aljuaid","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2025.117302_bib41","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231710171","article-title":"Antiviral activity of N1,N3-disubstituted uracil derivatives against SARS-CoV-2 variants of concern","volume":"23","author":"Siniavin","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2025.117302_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellin.2022.100046","article-title":"Screening of SARS-CoV-2 antivirals through a cell-based RNA-dependent RNA polymerase (RdRp) reporter assay","volume":"1","author":"Uppal","year":"2022","journal-title":"Cell Insight"},{"key":"10.1016\/j.ejmech.2025.117302_bib43","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1002\/adsc.202100082","article-title":"Direct, asymmetric synthesis of carbocycle\u2010fused uracils via [4+2] cycloadditions: a noncovalent organocatalysis approach","volume":"363","author":"Marcantonio","year":"2021","journal-title":"Adv. Synth. Catal."},{"key":"10.1016\/j.ejmech.2025.117302_bib44","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/adsc.202300045","article-title":"Mechanistic insights into the stepwise (4+2) cycloaddition toward chiral fused uracil derivatives","volume":"365","author":"Marcantonio","year":"2023","journal-title":"Adv. Synth. Catal."},{"key":"10.1016\/j.ejmech.2025.117302_bib45","doi-asserted-by":"crossref","first-page":"20055","DOI":"10.1002\/anie.202007509","article-title":"Unlocking access to enantiopure fused uracils by chemodivergent [4+2] cross\u2010cycloadditions: DFT\u2010supported Homo\u2010synergistic organocatalytic approach","volume":"59","author":"Curti","year":"2020","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2025.117302_bib46","first-page":"509","article-title":"Accessing chiral dihydro- and tetrahydroquinazoline-2,4-diones via [4+2]-Cycloadditions: from pioneering studies to asymmetric organocatalyzed syntheses","volume":"26","author":"Curti","year":"2023","journal-title":"Targets in Heterocyclic Systems"},{"key":"10.1016\/j.ejmech.2025.117302_bib47","doi-asserted-by":"crossref","DOI":"10.1002\/chem.202304001","article-title":"Shaping chirality via stereoselective, organocatalytic [4+2] cycloadditions involving heterocyclic ortho-quinodimethanes","volume":"30","author":"Marcantonio","year":"2024","journal-title":"Chem. Eur J."},{"key":"10.1016\/j.ejmech.2025.117302_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2022.105342","article-title":"SARS-CoV-2 Permissive glioblastoma cell line for high throughput antiviral screening","volume":"203","author":"Vanhulle","year":"2022","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2025.117302_bib49","unstructured":"The slight discrepancy between the two reported data referred to compound 10 against the 20A.EU2 strain (EC50=7.41 \u03bcM in Table 1, entry 12; EC50=16.6 \u03bcM in Table 2, entry 5) is quite common in such antiviral tests, where the same experimental setup is applied on different cells from the same cell line but on different time points (different passage). In fact, a slight difference in cell state (e.g. metabolism, expression of relevant entry receptors, etc.) can affect the efficiency of virus uptake and replication, resulting in some change in susceptibility to the antiviral drugs."},{"key":"10.1016\/j.ejmech.2025.117302_bib50","article-title":"Structural basis of SARS-CoV-2 polymerase inhibition by favipiravir","volume":"2","author":"Peng","year":"2021","journal-title":"Innovation"},{"key":"10.1016\/j.ejmech.2025.117302_bib51","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2020.e04502","article-title":"SARS-CoV-2 RNA Dependent RNA polymerase (RdRp) \u2013 a drug repurposing study","volume":"6","author":"Ahmad","year":"2020","journal-title":"Heliyon"},{"key":"10.1016\/j.ejmech.2025.117302_bib52","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1021\/ct400045d","article-title":"Explicit ligand hydration shells improve the correlation between MM-PB\/GBSA binding energies and experimental activities","volume":"9","author":"Maffucci","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.ejmech.2025.117302_bib53","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1021\/acs.jcim.6b00196","article-title":"Improved computation of Protein\u2212Protein relative binding energies with the nwat-MMGBSA method","volume":"56","author":"Maffucci","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2025.117302_bib54","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fchem.2018.00043","article-title":"An efficient implementation of the nwat-MMGBSA method to rescore docking results in medium-throughput virtual screenings","volume":"6","author":"Maffucci","year":"2018","journal-title":"Front. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib55","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.cell.2020.07.033","article-title":"Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex","volume":"182","author":"Chen","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2025.117302_bib56","doi-asserted-by":"crossref","first-page":"7821","DOI":"10.1039\/c0cp00111b","article-title":"The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building","volume":"12","author":"Dupradeau","year":"2010","journal-title":"Phys. Chem. Chem. Phys."},{"key":"10.1016\/j.ejmech.2025.117302_bib57","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115118","article-title":"Identification of a short ACE2-derived stapled peptide targeting the SARS-CoV-2 spike protein","volume":"249","author":"Calugi","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117302_bib58","doi-asserted-by":"crossref","first-page":"8765","DOI":"10.3390\/ijms24108765","article-title":"Novel polymyxin-inspired peptidomimetics targeting the SARS-CoV-2 spike:hACE2 interface","volume":"24","author":"Bugatti","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2025.117302_bib59","doi-asserted-by":"crossref","DOI":"10.1063\/1.3149788","article-title":"Langevin thermostat for rigid body dynamics","volume":"130","author":"Davidchack","year":"2009","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.ejmech.2025.117302_bib60","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular dynamics with coupling to an external bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.ejmech.2025.117302_bib61","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J. Comput. Phys."},{"key":"10.1016\/j.ejmech.2025.117302_bib62","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2144\/btn-2022-0018","article-title":"Intracellular flow cytometry complements RT-qPCR detection of circulating SARS-CoV-2 variants of concern","volume":"72","author":"Vanhulle","year":"2022","journal-title":"Biotechniques"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425000674?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425000674?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:06:07Z","timestamp":1762265167000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425000674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":62,"alternative-id":["S0223523425000674"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117302","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The chiral 5,6-cyclohexane-fused uracil ring-system: A molecular platform with promising activity against SARS-CoV-2","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117302","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117302"}}