{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:19:16Z","timestamp":1788394756275,"version":"build-2803163510"},"reference-count":182,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.ejmech.2026.118828","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:22:00Z","timestamp":1775578920000},"page":"118828","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Macrocycles and stapled-peptides in the fight against SARS-CoV-2: a review"],"prefix":"10.1016","volume":"312","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-3321","authenticated-orcid":false,"given":"Santo","family":"Previti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Calcaterra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florenci V.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Di Chio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Calabr\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Ettari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zappal\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.118828_bib1","doi-asserted-by":"crossref","first-page":"5377","DOI":"10.1021\/acs.jmedchem.3c00134","article-title":"Macrocycles in drug discovery-learning from the past for the future","volume":"66","author":"Garcia Jimenez","year":"2023","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3390\/ph18050617","article-title":"Exploring macrocyclic chemical space: strategies and technologies for drug discovery","volume":"18","author":"Kim","year":"2025","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.ejmech.2026.118828_bib3","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/nrd2590","article-title":"The exploration of macrocycles for drug discovery--an underexploited structural class","volume":"7","author":"Driggers","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2026.118828_bib4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00044-025-03506-1","article-title":"Macrocyclization in medicinal chemistry: updated strategies and applications","volume":"35","author":"Darlami","year":"2026","journal-title":"Med. Chem. Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib5","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1021\/jm400887j","article-title":"Macrocyclic drugs and clinical candidates: what can medicinal chemists learn from their properties?","volume":"57","author":"Giordanetto","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116501","article-title":"Macrocyclization strategy for improving candidate profiles in medicinal chemistry","volume":"272","author":"Darlami","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib7","doi-asserted-by":"crossref","first-page":"11725","DOI":"10.1039\/D3CS01066J","article-title":"Recent advances in peptide macrocyclization strategies","volume":"53","author":"Fang","year":"2024","journal-title":"Chem. Soc. Rev."},{"key":"10.1016\/j.ejmech.2026.118828_bib8","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1002\/anie.200500368","article-title":"Palladium-catalyzed cross-coupling reactions in total synthesis","volume":"44","author":"Nicolaou","year":"2005","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"10.1016\/j.ejmech.2026.118828_bib9","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.1016\/S0040-4039(03)01408-4","article-title":"Studies on novel macrocyclization methods of cembrane-type diterpenoids: a stille cyclization approach to (\u00b1)-isocembrene","volume":"44","author":"Peng","year":"2003","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2026.118828_bib10","doi-asserted-by":"crossref","first-page":"8316","DOI":"10.1002\/anie.201002809","article-title":"Prins-type macrocyclizations as an efficient ring-closing strategy in natural product synthesis","volume":"49","author":"Crane","year":"2010","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"10.1016\/j.ejmech.2026.118828_bib11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature10563","article-title":"Synthesis of macrocyclic natural products by catalyst-controlled stereoselective ring-closing metathesis","volume":"479","author":"Yu","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118828_bib12","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1021\/acs.oprd.8b00093","article-title":"Ring-closing metathesis in pharmaceutical development: fundamentals, applications, and future directions","volume":"22","author":"Yu","year":"2018","journal-title":"Org. Process Res. Dev."},{"key":"10.1016\/j.ejmech.2026.118828_bib13","doi-asserted-by":"crossref","first-page":"5001","DOI":"10.1038\/s41467-022-32723-0","article-title":"Thiol-Yne click chemistry of acetylene-enabled macrocyclization","volume":"13","author":"Lu","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib14","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1039\/b907457k","article-title":"A click chemistry approach for the synthesis of macrocycles from aryl amide-based precursors directed by hydrogen bonding","volume":"7","author":"Zhu","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsb.2024.108118","article-title":"Studying protein-protein interactions: latest and most popular approaches","volume":"216","author":"Akbarzadeh","year":"2024","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib16","doi-asserted-by":"crossref","first-page":"10079","DOI":"10.1021\/acs.chemrev.0c00532","article-title":"Stapled helical peptides bearing different anchoring residues","volume":"120","author":"Li","year":"2020","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2026.118828_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107137","article-title":"Therapeutic stapled peptides: efficacy and molecular targets","volume":"203","author":"Li","year":"2024","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib18","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.csbj.2019.01.012","article-title":"Stapled peptides inhibitors: a new window for target drug discovery","volume":"17","author":"Ali","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.ejmech.2026.118828_bib19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41392-020-00315-3","article-title":"Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials","volume":"5","author":"Lu","year":"2020","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.ejmech.2026.118828_bib20","doi-asserted-by":"crossref","DOI":"10.1002\/cbic.202500052","article-title":"Recent chemical biology insights towards reversible stapled peptides","volume":"26","author":"Chen","year":"2025","journal-title":"Chembiochem"},{"key":"10.1016\/j.ejmech.2026.118828_bib21","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1080\/17460441.2024.2350568","article-title":"Innovative peptide architectures: advancements in foldamers and stapled peptides for drug discovery","volume":"19","author":"Dongrui","year":"2024","journal-title":"Expet Opin. Drug Discov."},{"key":"10.1016\/j.ejmech.2026.118828_bib22","doi-asserted-by":"crossref","first-page":"7322","DOI":"10.1038\/s41467-025-62344-2","article-title":"Universal peptide synthesis via solid-phase methods fused with chemputation","volume":"16","author":"Zero","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib23","doi-asserted-by":"crossref","first-page":"6275","DOI":"10.1021\/jm4011675","article-title":"Hydrocarbon-stapled peptides: principles, practice, and progress","volume":"57","author":"Walensky","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib24","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s11010-023-04848-3","article-title":"A brief overview of SARS-CoV-2 infection and its management strategies: a recent update","volume":"479","author":"Das","year":"2024","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.ejmech.2026.118828_bib25","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.3390\/v17081064","article-title":"SARS-CoV-2 infection and antiviral strategies: advances and limitations","volume":"17","author":"Soares","year":"2025","journal-title":"Viruses"},{"key":"10.1016\/j.ejmech.2026.118828_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.afres.2025.101424","article-title":"A comprehensive review on antiviral compounds and materials for active packaging development in the post-pandemic era","volume":"5","author":"Chen","year":"2025","journal-title":"Appl. Food Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib27","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.3390\/molecules27082523","article-title":"Advances in the development of SARS-CoV-2 Mpro inhibitors","volume":"27","author":"Agost-Beltran","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2026.118828_bib28","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.csbj.2022.01.026","article-title":"Advances in the development of therapeutic strategies against COVID-19 and perspectives in the drug design for emerging SARS-CoV-2 variants","volume":"20","author":"Yin","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.ejmech.2026.118828_bib29","doi-asserted-by":"crossref","first-page":"825","DOI":"10.3390\/pathogens13100825","article-title":"Advances in the search for SARS-CoV-2 Mpro and PLpro inhibitors","volume":"13","author":"Diogo","year":"2024","journal-title":"Pathogens"},{"key":"10.1016\/j.ejmech.2026.118828_bib30","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.01642-24","article-title":"Cathepsins in cellular entry of human pathogenic viruses","volume":"99","author":"Pathak","year":"2025","journal-title":"J. Virol."},{"key":"10.1016\/j.ejmech.2026.118828_bib31","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.3390\/biom15111530","article-title":"Beyond processing: furin as a central hub in viral pathogenesis and genetic susceptibility","volume":"15","author":"Silva-Rios","year":"2025","journal-title":"Biomolecules"},{"key":"10.1016\/j.ejmech.2026.118828_bib32","doi-asserted-by":"crossref","DOI":"10.1002\/mco2.151","article-title":"The SARS-CoV-2 main protease (Mpro): structure, function, and emerging therapies for COVID-19","volume":"3","author":"Hu","year":"2022","journal-title":"MedComm"},{"key":"10.1016\/j.ejmech.2026.118828_bib33","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1016\/j.apsb.2025.07.001","article-title":"The role of SARS-CoV-2 main protease in innate immune regulation: from molecular mechanisms to therapeutic implications","volume":"15","author":"Gao","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.ejmech.2026.118828_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115772","article-title":"Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: a comprehensive review","volume":"260","author":"Li","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib35","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1038\/s42003-024-07138-w","article-title":"Allostery in homodimeric SARS-CoV-2 main protease","volume":"7","author":"Fornasier","year":"2024","journal-title":"Commun. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib42","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41467-023-44621-0","article-title":"Multiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design","volume":"15","author":"Funk","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib36","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1021\/acschembio.4c00096","article-title":"High-resolution substrate specificity profiling of SARS-CoV-2 Mpro; comparison to SARS-CoV Mpro","volume":"19","author":"Yaghi","year":"2024","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib37","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2023.1251705","article-title":"Characterization of host substrates of SARS-CoV-2 main protease","volume":"14","author":"Melano","year":"2023","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.ejmech.2026.118828_bib38","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1021\/jacsau.4c00508","article-title":"A structural comparison of oral SARS-CoV-2 drug candidate ibuzatrelvir complexed with the main protease (Mpro) of SARS-CoV-2 and MERS-CoV","volume":"4","author":"Chen","year":"2024","journal-title":"JACS Au"},{"key":"10.1016\/j.ejmech.2026.118828_bib39","doi-asserted-by":"crossref","DOI":"10.1080\/14756366.2025.2460045","article-title":"Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds","volume":"40","author":"Atatreh","year":"2025","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib40","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1021\/acsmedchemlett.4c00146","article-title":"SARS-CoV-2 main protease inhibitors that leverage unique interactions with the solvent exposed S3 site of the enzyme","volume":"15","author":"Blankenship","year":"2024","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118828_bib41","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.3390\/biom13091339","article-title":"Recent advances in SARS-CoV-2 main protease inhibitors: from nirmatrelvir to future perspectives","volume":"13","author":"Citarella","year":"2023","journal-title":"Biomolecules"},{"key":"10.1016\/j.ejmech.2026.118828_bib43","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118828_bib44","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/s42003-025-08487-w","article-title":"Characterization of an unusual SARS-CoV-2 main protease natural variant exhibiting resistance to nirmatrelvir and ensitrelvir","volume":"8","author":"Bhandari","year":"2025","journal-title":"Commun. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2024.109344","article-title":"SARS-CoV-2 main protease (M-pro) mutational profiling: an insight into mutation coldspots","volume":"184","author":"Garcia-Segura","year":"2025","journal-title":"Comput. Biol. Med."},{"key":"10.1016\/j.ejmech.2026.118828_bib46","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.02624-24","article-title":"Structural basis for varying drug resistance of SARS-CoV-2 Mpro E166 variants","volume":"16","author":"Esler","year":"2025","journal-title":"mBio"},{"key":"10.1016\/j.ejmech.2026.118828_bib47","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113530","article-title":"A cyclic peptide inhibitor of the SARS-CoV-2 main protease","volume":"221","author":"Kreutzer","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib48","doi-asserted-by":"crossref","first-page":"12997","DOI":"10.1073\/pnas.1601327113","article-title":"SARS-CoV 3CL protease cleaves its C-Terminal autoprocessing site by novel subsite cooperativity","volume":"113","author":"Muramatsu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2026.118828_bib49","doi-asserted-by":"crossref","first-page":"5047","DOI":"10.1038\/s41467-020-18709-w","article-title":"Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease","volume":"11","author":"Douangamath","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib50","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved \u03b1-ketoamide inhibitors","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118828_bib51","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.105363","article-title":"Discovery of novel oxazole-based macrocycles as anti-coronaviral agents targeting SARS-CoV-2 main protease","volume":"116","author":"Al-Wahaibi","year":"2021","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib52","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.2026.118828_bib53","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1039\/D1SC06750H","article-title":"Antiviral cyclic peptides targeting the main protease of SARS-CoV-2","volume":"13","author":"Johansen-Leete","year":"2022","journal-title":"Chem. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib54","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.biopha.2018.09.097","article-title":"Cell penetrating peptides: a concise review with emphasis on biomedical applications","volume":"108","author":"Derakhshankhah","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2026.118828_bib55","first-page":"126","article-title":"Cell-penetrating and cell-targeting peptides in drug delivery","volume":"1786","author":"Vives","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejmech.2026.118828_bib56","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41557-023-01205-1","article-title":"In vitro selection of macrocyclic peptide inhibitors containing cyclic \u03b32,4-amino acids targeting the SARS-CoV-2 main protease","volume":"15","author":"Miura","year":"2023","journal-title":"Nat. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib57","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00726-011-0893-3","article-title":"Foldamers containing \u03b3-amino acid residues or their analogues: structural features and applications","volume":"41","author":"Bouillere","year":"2011","journal-title":"Amino Acids"},{"key":"10.1016\/j.ejmech.2026.118828_bib58","doi-asserted-by":"crossref","first-page":"6925","DOI":"10.1039\/D5CC00746A","article-title":"Stereochemical matching determines both helix type and handedness in \u03b1\/\u03b3-peptides with a cyclic-constrained \u03b3-amino acid","volume":"61","author":"Liu","year":"2025","journal-title":"Chem. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib59","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1039\/C6OB00380J","article-title":"Structural and morphological diversity of self-assembled synthetic \u03b3-amino acid containing peptides","volume":"14","author":"Konda","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib60","doi-asserted-by":"crossref","first-page":"9718","DOI":"10.1021\/jm5010896","article-title":"Peptides containing \u03b2-amino acid patterns: challenges and successes in medicinal chemistry","volume":"57","author":"Cabrele","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib61","doi-asserted-by":"crossref","DOI":"10.1093\/bulcsj\/uoae018","article-title":"Cyclic \u03b22,3-amino acids improve the serum stability of macrocyclic peptide inhibitors targeting the SARS-CoV-2 main protease","volume":"97","author":"Miura","year":"2024","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"10.1016\/j.ejmech.2026.118828_bib63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s40262-023-01339-y","article-title":"A comprehensive review of the clinical pharmacokinetics, pharmacodynamics, and drug interactions of nirmatrelvir\/ritonavir","volume":"63","author":"Gerhart","year":"2024","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.ejmech.2026.118828_bib64","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2024.117846","article-title":"Discovery of macrocyclic covalent inhibitors for severe acute respiratory syndrome coronavirus 2 3CL protease","volume":"111","author":"Tang","year":"2024","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118828_bib65","doi-asserted-by":"crossref","first-page":"20258","DOI":"10.1021\/acs.jmedchem.4c01639","article-title":"De novo discovery of a noncovalent cell-penetrating bicyclic peptide inhibitor targeting SARS-CoV-2 main protease","volume":"67","author":"Tan","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib66","doi-asserted-by":"crossref","first-page":"8315","DOI":"10.1021\/acs.jmedchem.5b00258","article-title":"Applications of fluorine in medicinal chemistry","volume":"58","author":"Gillis","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib67","doi-asserted-by":"crossref","first-page":"19623","DOI":"10.1021\/acs.jmedchem.4c02009","article-title":"Rational design of macrocyclic noncovalent inhibitors of SARS-CoV-2 Mpro from a DNA-encoded chemical library screening hit that demonstrate potent inhibition against pan-coronavirus homologues and nirmatrelvir-resistant variants","volume":"67","author":"Wang","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib68","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1021\/acsptsci.1c00118","article-title":"DNA-encoded chemical libraries: a comprehensive review with successful stories and future challenges","volume":"4","author":"Gironda-Martinez","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib69","doi-asserted-by":"crossref","first-page":"6578","DOI":"10.1021\/acs.jmedchem.9b01782","article-title":"DNA-encoded library screening as core platform technology in drug discovery: its synthetic method development and applications in DEL synthesis","volume":"63","author":"Song","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib70","doi-asserted-by":"crossref","first-page":"8757","DOI":"10.1021\/acs.jmedchem.4c00053","article-title":"Macrocyclic azapeptide nitriles: structure-based discovery of potent SARS-CoV-2 main protease inhibitors as antiviral drugs","volume":"67","author":"Breidenbach","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib71","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41579-025-01185-8","article-title":"SARS-CoV-2 spike protein: structure, viral entry and variants","volume":"23","author":"Chen","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ejmech.2026.118828_bib72","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/s41467-022-28768-w","article-title":"Evolution of the SARS-CoV-2 spike protein in the human host","volume":"13","author":"Wrobel","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib73","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/cbin.12130","article-title":"What makes SARS-CoV-2 unique? Focusing on the spike protein","volume":"48","author":"Qian","year":"2024","journal-title":"Cell Biol. Int."},{"key":"10.1016\/j.ejmech.2026.118828_bib74","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsb.2025.108229","article-title":"Insights into the pathogenic mechanisms associated with the SARS-CoV-2 spike protein","volume":"217","author":"Argyrou","year":"2025","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib75","doi-asserted-by":"crossref","DOI":"10.1016\/j.virol.2024.110383","article-title":"Architects of infection: a structural overview of SARS-related coronavirus spike glycoproteins","volume":"604","author":"Hills","year":"2025","journal-title":"Virology"},{"key":"10.1016\/j.ejmech.2026.118828_bib76","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1007\/s11033-022-08193-4","article-title":"Interactions of angiotensin-converting enzyme-2 (ACE2) and SARS-CoV-2 spike receptor-binding domain (RBD): a structural perspective","volume":"50","author":"Borkotoky","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.ejmech.2026.118828_bib77","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1002\/prot.26855","article-title":"Structural analysis of the SARS-CoV-2 spike N-terminal domain across wild-type and recent variants: a comparative study","volume":"93","author":"Quaranta","year":"2025","journal-title":"Proteins"},{"key":"10.1016\/j.ejmech.2026.118828_bib78","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012383","article-title":"The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2","volume":"20","author":"Guenthoer","year":"2024","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ejmech.2026.118828_bib79","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3390\/v17050691","article-title":"Receptor binding for the entry mechanisms of SARS-CoV-2: insights from the original strain and emerging variants","volume":"17","author":"Mahdi","year":"2025","journal-title":"Viruses"},{"key":"10.1016\/j.ejmech.2026.118828_bib80","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41392-023-01472-x","article-title":"Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines","volume":"8","author":"Guo","year":"2023","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.ejmech.2026.118828_bib81","doi-asserted-by":"crossref","DOI":"10.1080\/22221751.2023.2220582","article-title":"SARS-CoV-2 spike S2-specific neutralizing antibodies","volume":"12","author":"Li","year":"2023","journal-title":"Emerg. Microb. Infect."},{"key":"10.1016\/j.ejmech.2026.118828_bib82","doi-asserted-by":"crossref","DOI":"10.1016\/j.jinf.2024.106121","article-title":"Molecular insights into the adaptive evolution of SARS-CoV-2 spike protein","volume":"88","author":"Yao","year":"2024","journal-title":"J. Infect."},{"key":"10.1016\/j.ejmech.2026.118828_bib83","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1021\/acsinfecdis.1c00433","article-title":"Structure and mutations of SARS-CoV-2 spike protein: a focused overview","volume":"8","author":"Mehra","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.ejmech.2026.118828_bib84","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/med.21941","article-title":"Research progress in spike mutations of SARS-CoV-2 variants and vaccine development","volume":"43","author":"He","year":"2023","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118828_bib85","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.3390\/biom15111489","article-title":"Structural insights into the SARS-CoV-2 spike protein and its implications for antibody resistance","volume":"15","author":"Yamamoto","year":"2025","journal-title":"Biomolecules"},{"key":"10.1016\/j.ejmech.2026.118828_bib86","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.00922-23","article-title":"Mutations in S2 subunit of SARS-CoV-2 omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity","volume":"97","author":"Kumar","year":"2023","journal-title":"J. Virol."},{"key":"10.1016\/j.ejmech.2026.118828_bib87","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02451-20","article-title":"Stapled peptides based on human angiotensin-converting enzyme 2 (ACE2) potently inhibit SARS-CoV-2 infection in vitro","volume":"11","author":"Curreli","year":"2020","journal-title":"mBio"},{"key":"10.1016\/j.ejmech.2026.118828_bib88","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1021\/acschembio.6b00386","article-title":"Protease-resistant and cell-permeable double-stapled peptides targeting the Rab8a GTPase","volume":"11","author":"Cromm","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib89","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1021\/acscentsci.0c01708","article-title":"Discovery of cyclic peptide ligands to the SARS-CoV-2 spike protein using mRNA display","volume":"7","author":"Norman","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib90","doi-asserted-by":"crossref","first-page":"7282","DOI":"10.1021\/acs.jcim.3c00803","article-title":"Exploring the fatty acid binding pocket in the SARS-CoV-2 spike protein - confirmed and potential ligands","volume":"63","author":"Queiros-Reis","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2026.118828_bib91","doi-asserted-by":"crossref","DOI":"10.1002\/pep2.24217","article-title":"Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalization","volume":"113","author":"Morgan","year":"2021","journal-title":"Pept. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib92","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","article-title":"Structural basis of receptor recognition by SARS-CoV-2","volume":"581","author":"Shang","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118828_bib93","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.3390\/biomedicines12102361","article-title":"Peptide-based inhibitors of protein-protein interactions (PPIs): a case study on the interaction between SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 (hACE2)","volume":"12","author":"Rakhmetullina","year":"2024","journal-title":"Biomedicines"},{"key":"10.1016\/j.ejmech.2026.118828_bib94","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1039\/D0CC08387A","article-title":"Targeting SARS-CoV-2 spike protein by stapled hACE2 peptides","volume":"57","author":"Maas","year":"2021","journal-title":"Chem. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib95","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/j.csbj.2022.04.030","article-title":"SARS-CoV-2 pan-variant inhibitory peptides deter S1-ACE2 interaction and neutralize delta and omicron pseudoviruses","volume":"20","author":"Shah","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.ejmech.2026.118828_bib96","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1007\/s40121-021-00525-4","article-title":"Efficacy of bamlanivimab\/etesevimab and casirivimab\/imdevimab in preventing progression to severe COVID-19 and role of variants of concern","volume":"10","author":"Falcone","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"10.1016\/j.ejmech.2026.118828_bib97","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1126\/science.abb7269","article-title":"A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV","volume":"368","author":"Yuan","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118828_bib98","doi-asserted-by":"crossref","first-page":"17486","DOI":"10.1021\/acs.jmedchem.1c01681","article-title":"Stapled peptides targeting SARS-CoV-2 spike protein HR1 inhibit the fusion of virus to its cell receptor","volume":"64","author":"Zheng","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib99","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/s41423-020-0374-2","article-title":"Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein","volume":"17","author":"Xia","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.ejmech.2026.118828_bib100","doi-asserted-by":"crossref","first-page":"12634","DOI":"10.1039\/D2SC04058A","article-title":"Pattern enrichment analysis for phage selection of stapled peptide ligands","volume":"13","author":"Miki","year":"2022","journal-title":"Chem. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib101","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-01225-2","article-title":"A high-throughput pipeline for design and selection of peptides targeting the SARS-Cov-2 spike protein","volume":"11","author":"Wolfe","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2026.118828_bib102","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1021\/acschembio.2c00565","article-title":"Novel regioselective approach to cyclize phage-displayed peptides in combination with epitope-directed selection to identify a potent neutralizing macrocyclic peptide for SARS-CoV-2","volume":"17","author":"Hampton","year":"2022","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib103","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41421-022-00455-6","article-title":"A novel cyclic \u03b3-AApeptide-based long-acting pan-coronavirus fusion inhibitor with potential oral bioavailability by targeting two sites in spike protein","volume":"8","author":"Xue","year":"2022","journal-title":"Cell Discov."},{"key":"10.1016\/j.ejmech.2026.118828_bib104","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1515\/hsz-2021-0426","article-title":"Atomistic insight into the essential binding event of ACE2-derived peptides to the SARS-CoV-2 spike protein","volume":"403","author":"Sarto","year":"2022","journal-title":"Biol. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib105","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.virol.2006.01.029","article-title":"Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor","volume":"350","author":"Han","year":"2006","journal-title":"Virology"},{"key":"10.1016\/j.ejmech.2026.118828_bib106","doi-asserted-by":"crossref","DOI":"10.3389\/fddsv.2022.1085701","article-title":"Discovery of novel spike\/ACE2 inhibitory macrocycles using reinforcement learning","volume":"2","author":"Shapira","year":"2022","journal-title":"Front. Drug Discov."},{"key":"10.1016\/j.ejmech.2026.118828_bib107","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2026.118828_bib108","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1039\/D3MD00222E","article-title":"De novo design of a stapled peptide targeting SARS-CoV-2 spike protein receptor-binding domain","volume":"14","author":"Thakkar","year":"2023","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib109","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.cell.2020.03.045","article-title":"Structural and functional basis of SARS-CoV-2 entry by using human ACE2","volume":"181","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2026.118828_bib110","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2303292120","article-title":"A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein","volume":"120","author":"Thijssen","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2026.118828_bib111","doi-asserted-by":"crossref","first-page":"22665","DOI":"10.1021\/acsomega.3c01436","article-title":"Antiviral activity against SARS-CoV-2 of conformationally constrained helical peptides derived from angiotensin-converting enzyme 2","volume":"8","author":"Quagliata","year":"2023","journal-title":"ACS Omega"},{"key":"10.1016\/j.ejmech.2026.118828_bib112","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1038\/s41467-026-68462-9","article-title":"Intranasal administration of broad-spectrum macrocyclic peptide inhibitor protects against SARS-CoV-2 Omicron variants","volume":"17","author":"Wang","year":"2026","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib113","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2221324120","article-title":"Evolution of coronavirus frameshifting elements: competing stem networks explain conservation and variability","volume":"120","author":"Yan","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2026.118828_bib114","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.tips.2025.04.003","article-title":"The frameshifting element in coronaviruses: structure, function, and potential as a therapeutic target","volume":"46","author":"Li","year":"2025","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib115","doi-asserted-by":"crossref","first-page":"10741","DOI":"10.1074\/jbc.AC120.013449","article-title":"Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2)","volume":"295","author":"Kelly","year":"2020","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib116","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.abf3546","article-title":"Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome","volume":"372","author":"Bhatt","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118828_bib117","doi-asserted-by":"crossref","first-page":"11133","DOI":"10.1073\/pnas.162223099","article-title":"A -1 ribosomal frameshift element that requires base pairing across four kilobases suggests a mechanism of regulating ribosome and replicase traffic on a viral RNA","volume":"99","author":"Barry","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2026.118828_bib118","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41392-025-02277-w","article-title":"Stem loop binding protein promotes SARS-CoV-2 replication via -1 programmed ribosomal frameshifting","volume":"10","author":"Chen","year":"2025","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.ejmech.2026.118828_bib119","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3390\/v14020177","article-title":"Identifying inhibitors of -1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses","volume":"14","author":"Munshi","year":"2022","journal-title":"Viruses"},{"key":"10.1016\/j.ejmech.2026.118828_bib120","doi-asserted-by":"crossref","first-page":"7193","DOI":"10.1038\/s41467-021-27431-0","article-title":"The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting","volume":"12","author":"Zimmer","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.118828_bib121","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2023051118","article-title":"Restriction of SARS-CoV-2 replication by targeting programmed -1 ribosomal frameshifting","volume":"118","author":"Sun","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2026.118828_bib122","doi-asserted-by":"crossref","first-page":"6190","DOI":"10.1021\/acs.jcim.4c00758","article-title":"Novel inhibitors of SARS-CoV-2 RNA identified through virtual screening","volume":"64","author":"Mathez","year":"2024","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2026.118828_bib123","doi-asserted-by":"crossref","first-page":"5843","DOI":"10.1016\/j.jmb.2020.09.006","article-title":"Anti-frameshifting ligand active against SARS coronavirus-2 is resistant to natural mutations of the frameshift-stimulatory pseudoknot","volume":"432","author":"Neupane","year":"2020","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib124","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1261\/rna.078825.121","article-title":"Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot","volume":"28","author":"Jones","year":"2022","journal-title":"RNA"},{"key":"10.1016\/j.ejmech.2026.118828_bib125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2024.2433830","article-title":"Decoding the genome of SARS-CoV-2: a pathway to drug development through translation inhibition","volume":"21","author":"Wu","year":"2024","journal-title":"RNA Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib126","doi-asserted-by":"crossref","first-page":"19520","DOI":"10.1039\/D4SC04026K","article-title":"Cyclic peptides targeting the SARS-CoV-2 programmed ribosomal frameshifting RNA from a multiplexed phage display library","volume":"15","author":"Iannuzzelli","year":"2024","journal-title":"Chem. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib127","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1021\/acscentsci.9b00927","article-title":"MOrPH-PhD: an integrated phage display platform for the discovery of functional genetically encoded peptide macrocycles","volume":"6","author":"Owens","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib128","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1093\/nar\/gks1361","article-title":"RNA dimerization plays a role in ribosomal frameshifting of the SARS coronavirus","volume":"41","author":"Ishimaru","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib129","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.3390\/v17111405","article-title":"Mechanisms of cell\u2013cell fusion in SARS-CoV-2: an evolving strategy for transmission and immune evasion","volume":"17","author":"Chiang","year":"2025","journal-title":"Viruses"},{"key":"10.1016\/j.ejmech.2026.118828_bib130","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00002-21","article-title":"SARS-CoV-2 and SARS-CoV spike-mediated cell-cell fusion differ in their requirements for receptor expression and proteolytic activation","volume":"95","author":"Hornich","year":"2021","journal-title":"J. Virol."},{"key":"10.1016\/j.ejmech.2026.118828_bib131","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.3390\/ijms23094576","article-title":"The endolysosomal system: the acid test for SARS-CoV-2","volume":"23","author":"Cesar-Silva","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib132","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2020.104792","article-title":"Coronavirus membrane fusion mechanism offers a potential target for antiviral development","volume":"178","author":"Tang","year":"2020","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib133","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.addr.2020.11.007","article-title":"Peptide and peptide-based inhibitors of SARS-CoV-2 entry","volume":"167","author":"Schutz","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejmech.2026.118828_bib134","doi-asserted-by":"crossref","first-page":"7276","DOI":"10.3390\/ijms26157276","article-title":"Membrane-targeting antivirals","volume":"26","author":"Krasilnikov","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib135","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: implications for SARS-CoV-2","volume":"19","author":"V'Kovski","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ejmech.2026.118828_bib136","doi-asserted-by":"crossref","DOI":"10.1002\/mco2.666","article-title":"Development of potent pan-coronavirus fusion inhibitors with a new design strategy","volume":"5","author":"Zhu","year":"2024","journal-title":"MedComm"},{"key":"10.1016\/j.ejmech.2026.118828_bib137","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2023.105571","article-title":"Design and characterization of novel SARS-CoV-2 fusion inhibitors with N-terminally extended HR2 peptides","volume":"212","author":"Hu","year":"2023","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib138","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1080\/22221751.2022.2098060","article-title":"SARS-CoV-2 fusion-inhibitory lipopeptides maintain high potency against divergent variants of concern including omicron","volume":"11","author":"Zhu","year":"2022","journal-title":"Emerg. Microb. Infect."},{"key":"10.1016\/j.ejmech.2026.118828_bib139","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2023.105575","article-title":"Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: new tricks for old dogs","volume":"212","author":"Shekunov","year":"2023","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib140","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijantimicag.2020.106218","article-title":"LPD-12: a promising lipopeptide to control COVID-19","volume":"57","author":"Chowdhury","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"10.1016\/j.ejmech.2026.118828_bib141","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2022.866474","article-title":"Anti-fungal drug anidulafungin inhibits SARS-CoV-2 spike-induced syncytia formation by targeting ACE2-spike protein interaction","volume":"13","author":"Ahamad","year":"2022","journal-title":"Front. Genet."},{"key":"10.1016\/j.ejmech.2026.118828_bib142","doi-asserted-by":"crossref","first-page":"14067","DOI":"10.1080\/07391102.2021.2000498","article-title":"Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2","volume":"40","author":"Dey","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.ejmech.2026.118828_bib143","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3390\/toxics10090521","article-title":"Caspofungin-induced cardiotoxicity in patients treating for candidemia","volume":"10","author":"Sattarzadeh Badkoubeh","year":"2022","journal-title":"Toxics"},{"key":"10.1016\/j.ejmech.2026.118828_bib144","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-68626-7","article-title":"Caspofungin induces the release of Ca2+ ions from internal stores by activating ryanodine receptor-dependent pathways in human tracheal epithelial cells","volume":"10","author":"Muller","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2026.118828_bib145","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.micinf.2004.04.003","article-title":"Paul Ehrlich--in search of the magic bullet","volume":"6","author":"Winau","year":"2004","journal-title":"Microb. Infect."},{"key":"10.1016\/j.ejmech.2026.118828_bib146","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2174\/1568026616666160927160620","article-title":"Hybrid compounds as direct multitarget ligands: a review","volume":"17","author":"de Oliveira Pedrosa","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib147","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.2174\/1568026616666160927151144","article-title":"Dual-acting of hybrid compounds - a new dawn in the discovery of multi-target drugs: lead generation approaches","volume":"17","author":"Abdolmaleki","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib148","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40169-017-0181-2","article-title":"A Perspective on multi-target drug discovery and design for complex diseases","volume":"7","author":"Ramsay","year":"2018","journal-title":"Clin. Transl. Med."},{"key":"10.1016\/j.ejmech.2026.118828_bib149","doi-asserted-by":"crossref","first-page":"11522","DOI":"10.1021\/acs.jmedchem.4c00384","article-title":"New strategies for responding to SARS-CoV-2: the present and future of dual-target drugs","volume":"67","author":"Zhang","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib150","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s41401-021-00668-7","article-title":"A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors","volume":"43","author":"Ren","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.ejmech.2026.118828_bib151","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1021\/jacs.4c11620","article-title":"Dual inhibitors of SARS-CoV-2 3CL protease and human cathepsin L containing glutamine isosteres are anti-CoV-2 agents","volume":"147","author":"Kumar","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2026.118828_bib152","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1021\/acsmedchemlett.3c00562","article-title":"Identification of dual inhibitors targeting main protease (Mpro) and cathepsin L as potential anti-SARS-CoV-2 agents","volume":"15","author":"Previti","year":"2024","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118828_bib153","doi-asserted-by":"crossref","first-page":"21035","DOI":"10.1021\/jacs.2c04626","article-title":"Dual inhibitors of main protease (MPro) and cathepsin L as potent antivirals against SARS-CoV2","volume":"144","author":"Mondal","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2026.118828_bib154","article-title":"MPI8 is potent against SARS-CoV-2 by inhibiting dually and selectively the SARS-CoV-2 main protease and the host cathepsin L","volume":"17","author":"Ma","year":"2022","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2026.118828_bib155","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116671","article-title":"Novel compounds with dual inhibition activity against SARS-CoV-2 critical enzymes RdRp and human TMPRSS2","volume":"276","author":"Soliman","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib156","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2021.128099","article-title":"Promising anti-SARS-CoV-2 drugs by effective dual targeting against the viral and host proteases","volume":"43","author":"Elseginy","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118828_bib157","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.omtn.2021.10.016","article-title":"Dual inhibition of TMPRSS2 and cathepsin B prevents SARS-CoV-2 infection in iPS cells","volume":"26","author":"Hashimoto","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.ejmech.2026.118828_bib158","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s42003-022-03090-9","article-title":"Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay","volume":"5","author":"Narayanan","year":"2022","journal-title":"Commun. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib159","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.crstbi.2020.12.001","article-title":"Dual targeting of 3CLpro and PLpro of SARS-CoV-2: a novel structure-based design approach to treat COVID-19","volume":"3","author":"Rajpoot","year":"2021","journal-title":"Curr. Res. Struct. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib160","doi-asserted-by":"crossref","DOI":"10.1016\/j.crchbi.2022.100023","article-title":"Discovery of diminazene as a dual inhibitor of SARS-CoV-2 human host proteases TMPRSS2 and furin using cell-based assays","volume":"2","author":"Xu","year":"2022","journal-title":"Curr. Res. Chem. Biol."},{"key":"10.1016\/j.ejmech.2026.118828_bib161","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2025.e41980","article-title":"SARS-CoV-2 drug resistance and therapeutic approaches","volume":"11","author":"Batool","year":"2025","journal-title":"Heliyon"},{"key":"10.1016\/j.ejmech.2026.118828_bib162","doi-asserted-by":"crossref","DOI":"10.1155\/2024\/9125398","article-title":"Challenges in emerging vaccines and future promising candidates against SARS-CoV-2 variants","volume":"2024","author":"Ghildiyal","year":"2024","journal-title":"J. Immunol. Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib163","first-page":"280","article-title":"An investigation of nirmatrelvir (Paxlovid) resistance in SARS-CoV-2 Mpro, ACS Bio","volume":"4","author":"Yaghi","year":"2024","journal-title":"Med. Chem. Au"},{"key":"10.1016\/j.ejmech.2026.118828_bib164","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00268-004-7818-1","article-title":"Roles of neuropilins in neuronal development, angiogenesis, and cancers","volume":"29","author":"Chen","year":"2005","journal-title":"World J. Surg."},{"key":"10.1016\/j.ejmech.2026.118828_bib165","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3390\/curroncol32040203","article-title":"Neuropilin-1: a multifaceted target for cancer therapy","volume":"32","author":"Varanasi","year":"2025","journal-title":"Curr. Oncol."},{"key":"10.1016\/j.ejmech.2026.118828_bib166","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Cantuti-Castelvetri","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118828_bib167","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009153","article-title":"The role of neuropilin-1 in COVID-19","volume":"17","author":"Mayi","year":"2021","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ejmech.2026.118828_bib168","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118828_bib169","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.3390\/jcm10132772","article-title":"The role of neuropilin-1 (NRP-1) in SARS-CoV-2 infection: review","volume":"10","author":"Gudowska-Sawczuk","year":"2021","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.ejmech.2026.118828_bib170","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.1037993","article-title":"Non-covalent cyclic peptides simultaneously targeting Mpro and NRP1 are highly effective against omicron BA.2.75","volume":"13","author":"Yin","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2026.118828_bib171","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2021.128333","article-title":"Challenges of short substrate analogues as SARS-CoV-2 main protease inhibitors","volume":"50","author":"Ullrich","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118828_bib172","doi-asserted-by":"crossref","first-page":"13493","DOI":"10.1074\/jbc.M512121200","article-title":"Characterization of a bicyclic peptide neuropilin-1 (NP-1) antagonist (EG3287) reveals importance of vascular endothelial growth factor exon 8 for NP-1 binding and role of NP-1 in KDR signaling","volume":"281","author":"Jia","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2026.118828_bib173","article-title":"Dual-targeting cyclic peptides of receptor-binding domain (RBD) and main protease (Mpro) as potential drug leads for the treatment of SARS-CoV-2 infection","volume":"13","author":"Xu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2026.118828_bib174","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"Lan","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118828_bib175","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.3390\/molecules27092723","article-title":"Drug repurposing for COVID-19: a review and a novel strategy to identify new targets and potential drug candidates","volume":"27","author":"Rodrigues","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2026.118828_bib176","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2020.104787","article-title":"The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro","volume":"178","author":"Caly","year":"2020","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2026.118828_bib177","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/cpt.1889","article-title":"The approved dose of ivermectin alone is not the ideal dose for the treatment of COVID-19","volume":"108","author":"Schmith","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.ejmech.2026.118828_bib178","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1016\/j.xphs.2020.08.024","article-title":"Development of a minimal physiologically-based pharmacokinetic model to simulate lung exposure in humans following oral administration of ivermectin for COVID-19 drug repurposing","volume":"109","author":"Jermain","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejmech.2026.118828_bib179","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41429-021-00491-6","article-title":"The mechanisms of action of ivermectin against SARS-CoV-2-an extensive review","volume":"75","author":"Zaidi","year":"2022","journal-title":"J. Antibiot."},{"key":"10.1016\/j.ejmech.2026.118828_bib180","first-page":"60","volume":"COVID 2","author":"Chable-Bessia","year":"2022"},{"key":"10.1016\/j.ejmech.2026.118828_bib181","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1039\/D4NA00361F","article-title":"A novel nanocomposite drug delivery system for SARS-CoV-2 infections","volume":"6","author":"Chintapula","year":"2024","journal-title":"Nanoscale Adv."},{"key":"10.1016\/j.ejmech.2026.118828_bib182","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1080\/17425247.2020.1813712","article-title":"Lipid-based nano delivery of Tat-peptide conjugated drug or vaccine-promising therapeutic strategy for SARS-CoV-2 treatment","volume":"17","author":"Ansari","year":"2020","journal-title":"Expet Opin. Drug Deliv."},{"key":"10.1016\/j.ejmech.2026.118828_bib183","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejps.2021.106094","article-title":"Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines","volume":"169","author":"Sadeghian","year":"2022","journal-title":"Eur. J. Pharmaceut. Sci."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426002734?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426002734?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:30:30Z","timestamp":1777509030000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426002734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":182,"alternative-id":["S0223523426002734"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118828","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Macrocycles and stapled-peptides in the fight against SARS-CoV-2: a review","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118828","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"118828"}}