{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:23:25Z","timestamp":1783981405414,"version":"3.55.0"},"reference-count":140,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Since there is an urgent need for novel treatments to combat the current coronavirus disease 2019 (COVID-19) pandemic, in silico molecular docking studies were implemented as an attempt to explore the ability of selected bioactive constituents of extra virgin olive oil (EVOO) to act as potent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antiviral compounds, aiming to explore their ability to interact with SARS-CoV-2 Spike key therapeutic target protein. Our results suggest that EVOO constituents display substantial capacity for binding and interfering with Spike (S) protein, both wild-type and mutant, via the receptor-binding domain (RBD) of Spike, or other binding targets such as angiotensin-converting enzyme 2 (ACE2) or the RBD-ACE2 protein complex, inhibiting the interaction of the virus with host cells. This in silico study provides useful insights for the understanding of the mechanism of action of the studied compounds at a molecular level. From the present study, it could be suggested that the studied active phytochemicals could potentially inhibit the Spike protein, contributing thus to the understanding of the role that they can play in future drug designing and the development of anti-COVID-19 therapeutics.<\/jats:p>","DOI":"10.3390\/molecules27217572","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T09:20:27Z","timestamp":1667553627000},"page":"7572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-1663","authenticated-orcid":false,"given":"Elena G.","family":"Geromichalou","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-4870","authenticated-orcid":false,"given":"George D.","family":"Geromichalos","sequence":"additional","affiliation":[{"name":"Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15171\/jhp.2018.01","article-title":"Medicinal plants: Past history and future perspective","volume":"7","author":"Lorigooini","year":"2018","journal-title":"J. Herbmed Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7224","DOI":"10.1016\/j.arabjc.2020.08.004","article-title":"Structure-based virtual screening and molecular dynamics of phytochemicals derived from Saudi medicinal plants to identify potential COVID-19 therapeutics","volume":"13","author":"Alamri","year":"2020","journal-title":"Arab. J. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mahmood, R.A., Hasan, A., Rahmatullah, M., Paul, A.K., Jahan, R., Jannat, K., Bondhon, T.A., Mahboob, T., Nissapatorn, V., and de Lourdes Pereira, M. (2022). Solanaceae family phytochemicals as inhibitors of 3C-Like protease of SARS-CoV-2: An in silico analysis. Molecules, 27.","DOI":"10.3390\/molecules27154739"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561334","DOI":"10.3389\/fphar.2020.561334","article-title":"Anti-SARS-CoV natural products with the potential to inhibit SARS-CoV-2 (COVID-19)","volume":"11","author":"Verma","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104062","DOI":"10.1016\/j.amsu.2022.104062","article-title":"Role of natural products towards the SARS-CoV-2: A critical review","volume":"80","author":"Raman","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.3389\/fphar.2020.01189","article-title":"Medicinal plants as sources of active molecules against COVID-19","volume":"11","author":"Benarba","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Muchtaridi, M., Fauzi, M., Khairul Ikram, N.K., Mohd Gazzali, A., and Wahab, H.A. (2020). Natural flavonoids as potential Angiotensin-Converting Enzyme 2 inhibitors for Anti-SARS-CoV-2. Molecules, 25.","DOI":"10.3390\/molecules25173980"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.apsb.2020.06.002","article-title":"Bioactive natural compounds against human coronaviruses: A review and perspective","volume":"10","author":"Xian","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Anand, A.V., Balamuralikrishnan, B., Kaviya, M., Bharathi, K., Parithathvi, A., Arun, M., and Dhama, K. (2021). Medicinal plants, phytochemicals, and herbs to combat viral pathogens including SARS-CoV-2. Molecules, 26.","DOI":"10.3390\/molecules26061775"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.18311\/jnr\/2020\/25278","article-title":"In silico screening of traditional herbal medicine derived chemical constituents for possible potential inhibition against SARS-CoV-2","volume":"20","author":"Srimathi","year":"2020","journal-title":"J. Nat. Remedies"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1080\/07391102.2020.1810778","article-title":"Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants\u2014Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi)\u2014A molecular docking study","volume":"40","author":"Shree","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17699","DOI":"10.1038\/s41598-020-74715-4","article-title":"Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2","volume":"10","author":"Basu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2217\/fvl-2020-0079","article-title":"Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-CoV-2 inhibitors","volume":"15","author":"Salman","year":"2020","journal-title":"Future Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1007\/s42535-020-00162-1","article-title":"Molecular docking analysis of selected phytochemicals against SARS-CoV-2 Mpro receptor","volume":"33","author":"Garg","year":"2020","journal-title":"Vegetos"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103936","DOI":"10.1016\/j.compbiomed.2020.103936","article-title":"In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19","volume":"124","author":"Vardhan","year":"2020","journal-title":"Comput. Biol. Med."},{"key":"ref_16","first-page":"4529","article-title":"In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking","volume":"24","author":"Joshi","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s13659-020-00250-4","article-title":"Natural products as potential leads against coronaviruses: Could they be encouraging structural models against SARS-CoV-2?","volume":"10","author":"Orhan","year":"2020","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Feng, T., Zhang, M., Xu, Q., Song, F., Wang, L., Gai, S., Tang, H., Wang, S., Zhou, L., and Li, H. (2022). Exploration of molecular targets and mechanisms of Chinese medicinal formula Acacia Catechu -Scutellariae Radix in the treatment of COVID-19 by a systems pharmacology strategy. Phytother. Res.","DOI":"10.1002\/ptr.7554"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2217\/fvl-2021-0171","article-title":"Andrographolide induces anti-SARS-CoV-2 response through host-directed mechanism: An in silico study","volume":"17","author":"Das","year":"2022","journal-title":"Future Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e11171","DOI":"10.7717\/peerj.11171","article-title":"A molecular dynamics simulation study of the ACE2 receptor with screened natural inhibitors to identify novel drug candidate against COVID-19","volume":"9","author":"Srivastava","year":"2021","journal-title":"PeerJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108185","DOI":"10.1016\/j.jmgm.2022.108185","article-title":"Molecular modelling identification of phytocompounds from selected African botanicals as promising therapeutics against druggable human host cell targets of SARS-CoV-2","volume":"114","author":"Uhomoibhi","year":"2022","journal-title":"J. Mol. Graph. Model."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s40495-021-00259-4","article-title":"Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua inhibit Spike protein of SARS-CoV-2 binding to ACE2 receptor: In silico approach","volume":"7","author":"Rolta","year":"2021","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Siddiqui, S., Upadhyay, S., Ahmad, R., Barkat, M.A., Jamal, A., Alothaim, A.S., Hassan, M.Z., Rahman, M.A., Arshad, M., and Ahamad, T. (2022). Interaction of bioactive compounds of Moringa oleifera leaves with SARS-CoV-2 proteins to combat COVID-19 pathogenesis: A phytochemical and in silico analysis. Appl. Biochem. Biotechnol., 1\u201327.","DOI":"10.1007\/s12010-022-04040-1"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rahayu, I., and Timotius, K.H. (2022). Phytochemical analysis, antimutagenic and antiviral activity of Moringa oleifera L. leaf infusion: In vitro and in silico studies. Molecules, 27.","DOI":"10.3390\/molecules27134017"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s00894-021-04816-y","article-title":"Molecular screening of glycyrrhizin-based inhibitors against ACE2 host receptor of SARS-CoV-2","volume":"27","author":"Ahmad","year":"2021","journal-title":"J. Mol. Model."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1007\/s00894-020-04599-8","article-title":"Molecular basis for drug repurposing to study the interface of the S protein in SARS-CoV-2 and human ACE2 through docking, characterization, and molecular dynamics for natural drug candidates","volume":"26","author":"Alazmi","year":"2020","journal-title":"J. Mol. Model."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.ijbiomac.2021.09.146","article-title":"Spike protein recognizer receptor ACE2 targeted identification of potential natural antiviral drug candidates against SARS-CoV-2","volume":"191","author":"Pokhrel","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100413","DOI":"10.1016\/j.jaim.2021.02.004","article-title":"In silico evaluation of the compounds of the ayurvedic drug, AYUSH-64, for the action against the SARS-CoV-2 main protease","volume":"13","author":"Ram","year":"2022","journal-title":"J. Ayurveda Integr. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.9734\/ajrid\/2020\/v4i430152","article-title":"Evaluation of phytochemicals of Cassia occidentalis L. for their binding affinities to SARS-CoV-2 3C-Like protease: An in silico approach","volume":"4","author":"Bondhon","year":"2020","journal-title":"Asian J. Res. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104359","DOI":"10.1016\/j.compbiomed.2021.104359","article-title":"Identification of novel compounds against three targets of SARS-CoV-2 coronavirus by combined virtual screening and supervised machine learning","volume":"133","author":"Kadioglu","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/j.1469-185X.2012.00229.x","article-title":"Primary domestication and early uses of the emblematic olive tree: Palaeobotanical, historical and molecular evidence from the Middle East","volume":"87","author":"Kaniewski","year":"2012","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18508","DOI":"10.3390\/ijms151018508","article-title":"Effects of the olive-derived polyphenol oleuropein on human health","volume":"15","author":"Barbaro","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1093\/jn\/130.12.2996","article-title":"Oleuropein, an antioxidant polyphenol from olive oil, is poorly absorbed from isolated perfused rat intestine","volume":"130","author":"Edgecombe","year":"2000","journal-title":"J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jsps.2010.05.005","article-title":"Cardioprotective and neuroprotective roles of oleuropein in olive","volume":"18","author":"Omar","year":"2010","journal-title":"Saudi Pharm. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3390\/ijms11020458","article-title":"Biological activities of phenolic compounds present in virgin olive oil","volume":"11","author":"Cicerale","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1161\/01.ATV.0000062884.69432.A0","article-title":"Olive oil and red wine antioxidant polyphenols inhibit endothelial activation","volume":"23","author":"Carluccio","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1211\/0022357991773258","article-title":"On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol","volume":"51","author":"Bisignano","year":"1999","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1079\/NRR200495","article-title":"The phenolic compounds of olive oil: Structure, biological activity and beneficial effects on human health","volume":"18","author":"Tripoli","year":"2005","journal-title":"Nutr. Res. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1039\/C6FO00958A","article-title":"Anti-cancer properties of olive oil secoiridoid phenols: A systematic review of in vivo studies","volume":"7","author":"Fabiani","year":"2016","journal-title":"Food Funct."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.phymed.2010.08.016","article-title":"Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: Comparison with Captopril","volume":"18","author":"Susalit","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10549-020-06054-x","article-title":"Oleuropein is a natural inhibitor of PAI-1-mediated proliferation in human ER-\/PR- breast cancer cells","volume":"186","author":"Tzekaki","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111621","DOI":"10.1016\/j.exger.2021.111621","article-title":"Extra Virgin Olive Oil consumption from mild cognitive impairment patients attenuates oxidative and nitrative stress reflecting on the reduction of the PARP levels and DNA damage","volume":"156","author":"Tzekaki","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s12967-014-0219-9","article-title":"Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: Focus on protection against cardiovascular and metabolic diseases","volume":"12","author":"Bulotta","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rigacci, S., and Stefani, M. (2016). Nutraceutical properties of olive oil polyphenols. An itinerary from cultured cells through animal models to humans. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060843"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lagouri, V. (2019). Olive Oil: Antioxidant Compounds and Their Potential Effects over Health. Functional Foods, IntechOpen.","DOI":"10.5772\/intechopen.73983"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1093\/bioinformatics\/btu426","article-title":"YASARA View-molecular graphics for all devices\u2014From smartphones to workstations","volume":"30","author":"Krieger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"117652","DOI":"10.1016\/j.lfs.2020.117652","article-title":"In silico studies on therapeutic agents for COVID-19: Drug repurposing approach","volume":"252","author":"Shah","year":"2020","journal-title":"Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"55","DOI":"10.21833\/ijaas.2022.02.006","article-title":"To explore the pharmacological mechanism of action using digital twin","volume":"9","author":"Rahman","year":"2022","journal-title":"Int. J. Adv. Appl. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"98","DOI":"10.31080\/ASMI.2021.04.0879","article-title":"Therapeutic potential of olive\u2019s bioactive compounds in COVID-19 disease management","volume":"4","author":"Chandrashekharaiah","year":"2021","journal-title":"Acta Sci. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Takeda, Y., Jamsransuren, D., Matsuda, S., Crea, R., and Ogawa, H. (2021). The SARS-CoV-2-Inactivating activity of hydroxytyrosol-rich aqueous Olive pulp extract (HIDROX\u00ae) and its use as a virucidal cream for topical application. Viruses, 13.","DOI":"10.3390\/v13020232"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Alkhatib, A. (2020). Antiviral functional foods and exercise lifestyle prevention of Coronavirus. Nutrients, 12.","DOI":"10.3390\/nu12092633"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1016\/j.sjbs.2021.02.058","article-title":"In silico analysis of quranic and prophetic medicinals plants for the treatment of infectious viral diseases including corona virus","volume":"5","author":"Mehmood","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1248\/cpb.49.1471","article-title":"In vitro evaluation of secoiridoid glucosides from the fruits of Ligustrum lucidum as antiviral agents","volume":"49","author":"Ma","year":"2001","journal-title":"Chem. Pharm. Bull."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hussain, T., Habib, A.H., Rafeeq, M.M., Alafnan, A., Khafagy, E.-S., Iqbal, D., Jamal, Q.M.S., Unissa, R., Sharma, D.C., and Moin, A. (2022). Oleuropein as a potent compound against neurological complications linked with COVID-19: A computational biology approach. Entropy, 24.","DOI":"10.3390\/e24070881"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41586-020-2571-7","article-title":"Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike","volume":"584","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1021\/acs.jpcb.2c02365","article-title":"Ionization of D571 is coupled with SARS-CoV-2 Spike up\/down equilibrium revealing the pH-dependent allosteric mechanism of Receptor-Binding Domains","volume":"126","author":"Tong","year":"2022","journal-title":"J. Phys. Chem. B"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10482","DOI":"10.1021\/acs.jpclett.0c02958","article-title":"Computational insights into the conformational accessibility and binding strength of SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2","volume":"11","author":"Peng","year":"2020","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41423-020-0400-4","article-title":"Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine","volume":"17","author":"Tai","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"592908","DOI":"10.3389\/fmicb.2020.592908","article-title":"Molecular docking reveals ivermectin and remdesivir as potential repurposed drugs against SARS-CoV-2","volume":"11","author":"Eweas","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1002\/jmv.27524","article-title":"Characterization of the novel SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern and its global perspective","volume":"94","author":"Saxena","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"879118","DOI":"10.3389\/fphar.2022.879118","article-title":"Olive leaves as a potential phytotherapy in the treatment of COVID-19 disease; A Mini-Review","volume":"13","author":"Abdelgawad","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"627767","DOI":"10.3389\/fmolb.2020.627767","article-title":"Molecular docking and molecular dynamics aided virtual search of OliveNet\u2122 directory for secoiridoids to combat SARS-CoV-2 infection and associated hyperinflammatory responses","volume":"7","author":"Thangavel","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2174\/1389201022666210412143553","article-title":"Olive oil consumption can prevent non-communicable diseases and COVID-19: A Review","volume":"23","author":"Majumder","year":"2022","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.antiviral.2009.03.002","article-title":"Mechanism of the antiviral effect of hydroxytyrosol on influenza virus appears to involve morphological change of the virus","volume":"83","author":"Yamada","year":"2009","journal-title":"Antiviral Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nrmicro2090","article-title":"The spike protein of SARS-CoV-a target for vaccine and therapeutic development","volume":"7","author":"Du","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.4155\/fmc-2020-0147","article-title":"Tackling SARS-CoV-2: Proposed targets and repurposed drugs","volume":"12","author":"Joshi","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/j.drudis.2020.06.017","article-title":"Discovering small-molecule therapeutics against SARS-CoV-2","volume":"25","author":"Tiwari","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM Structure of the 2019-NCoV Spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/acscentsci.0c01056","article-title":"Beyond Shielding: The roles of glycans in SARS-CoV-2 Spike protein","volume":"6","author":"Casalino","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_72","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":"ref_73","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1021\/acscentsci.0c01236","article-title":"Fighting COVID-19 using molecular dynamics simulations","volume":"6","author":"Arantes","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13967","DOI":"10.1073\/pnas.2008209117","article-title":"Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions","volume":"117","author":"Wang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.bpj.2020.10.036","article-title":"The flexibility of ACE2 in the context of SARS-CoV-2 infection","volume":"120","author":"Barros","year":"2021","journal-title":"Biophys. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bbrc.2020.10.102","article-title":"Evolution patterns of SARS-CoV-2: Snapshot on its genome variants","volume":"538","author":"Giovanetti","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"eabf3671","DOI":"10.1126\/sciadv.abf3671","article-title":"The SARS-CoV-2 spike variant D614G favors an open conformational state","volume":"7","author":"Mansbach","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1002\/jcc.26383","article-title":"Atomistic simulation reveals structural mechanisms underlying D614G spike glycoprotein-enhanced fitness in SARS-CoV-2","volume":"41","author":"Omotuyi","year":"2020","journal-title":"J. Comput. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"104773","DOI":"10.1016\/j.meegid.2021.104773","article-title":"Variants in ACE2; potential influences on virus infection and COVID-19 severity","volume":"90","author":"Bakhshandeh","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_80","first-page":"473248","article-title":"SARS-CoV-2 Omicron spike mediated immune escape and tropism shift","volume":"12","author":"Meng","year":"2021","journal-title":"bioRxiv"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4780","DOI":"10.1002\/jmv.27927","article-title":"Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) of SARS-CoV-2 spike infectivity and pathogenicity: A comparative sequence and structural-based computational assessment","volume":"94","author":"Kumar","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.coviro.2014.06.002","article-title":"Antiviral drugs specific for coronaviruses in preclinical development","volume":"8","author":"Adedeji","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.abc6952","article-title":"A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2","volume":"369","author":"Chi","year":"2020","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","article-title":"Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody","volume":"583","author":"Pinto","year":"2020","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.apsb.2020.02.008","article-title":"Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods","volume":"10","author":"Wu","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s40200-020-00546-9","article-title":"Drug repurposing using computational methods to identify therapeutic options for COVID-19","volume":"19","author":"Mahdian","year":"2020","journal-title":"J. Diab. Metab. Disord."},{"key":"ref_87","unstructured":"Sharanya, C.S., Gangadharan, A.K., Jayanandhan, A., Abdulhameed, S., and Madathilkovilakathu, H. (2020). Drug repurposing for COVID-19 from FDA approved and experiment stage drugs by in silico methods with SARS-CoV-2 Spike protein. Biol. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/jmv.21571","article-title":"Characterization of cytotoxic T-lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD-integrin-binding motif","volume":"81","author":"Poh","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11157","DOI":"10.1073\/pnas.1708727114","article-title":"Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion","volume":"114","author":"Walls","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1111\/j.1476-5381.2010.00750.x","article-title":"Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: Current status","volume":"160","author":"Ma","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_91","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":"ref_92","doi-asserted-by":"crossref","first-page":"104016","DOI":"10.1016\/j.jff.2020.104016","article-title":"Exploring the active compounds of traditional Mongolian medicine in intervention of novel Coronavirus (COVID-19) based on molecular docking method","volume":"71","author":"Yu","year":"2020","journal-title":"J. Func. Foods"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"104859","DOI":"10.1016\/j.phrs.2020.104859","article-title":"Candidate drugs against SARS-CoV-2 and COVID-19","volume":"157","author":"McKee","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10822-020-00356-4","article-title":"Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein","volume":"35","author":"Deganutti","year":"2021","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1097\/HJH.0000000000002829","article-title":"The interaction of the severe acute respiratory syndrome coronavirus 2 spike protein with drug-inhibited angiotensin converting enzyme 2 studied by molecular dynamics simulation","volume":"39","author":"Nami","year":"2021","journal-title":"J. Hypertens."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1161\/01.HYP.0000205833.89478.5b","article-title":"Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II","volume":"47","author":"Yamamoto","year":"2006","journal-title":"Hypertension"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2131\/jts.46.471","article-title":"A rapid screening assay for L452R and T478K spike mutations in SARS-CoV-2 Delta variant using high-resolution melting analysis","volume":"46","author":"Aoki","year":"2021","journal-title":"J. Toxicol. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s00894-021-04828-8","article-title":"Potential activity of Linezolid against SARS-CoV-2 using electronic and molecular docking study","volume":"27","author":"Morgon","year":"2021","journal-title":"J. Mol. Model."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00894-021-04833-x","article-title":"Luteolin: A blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics","volume":"27","author":"Shadrack","year":"2021","journal-title":"J. Mol. Model."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s00894-022-05059-1","article-title":"Different compounds against Angiotensin-Converting Enzyme 2 (ACE2) receptor potentially containing the infectivity of SARS-CoV-2: An in silico study","volume":"28","author":"Shahbazi","year":"2022","journal-title":"J. Mol. Model."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1126\/science.abn8863","article-title":"Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody","volume":"375","author":"Yin","year":"2022","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1126\/science.abh1139","article-title":"Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants","volume":"373","author":"Yuan","year":"2021","journal-title":"Science"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41586-020-03041-6","article-title":"Correlates of protection against SARS-CoV-2 in rhesus macaques","volume":"590","author":"McMahan","year":"2021","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41586-021-04385-3","article-title":"Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies","volume":"602","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1056\/NEJMc2119270","article-title":"Effectiveness of BNT162b2 vaccine against Omicron variant in South Africa","volume":"386","author":"Collie","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/pro.2279","article-title":"Role of loops connecting secondary structure elements in the stabilization of proteins isolated from thermophilic organisms","volume":"22","author":"Balasco","year":"2013","journal-title":"Protein Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"101212","DOI":"10.1016\/j.isci.2020.101212","article-title":"Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1\/S2 site","volume":"23","author":"Jaimes","year":"2020","journal-title":"iScience"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s00894-003-0168-3","article-title":"Structure-based method for analyzing protein-protein interfaces","volume":"10","author":"Gao","year":"2004","journal-title":"J. Mol. Model."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00894-011-1018-3","article-title":"Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease","volume":"18","author":"Singh","year":"2012","journal-title":"J. Mol. Model."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41586-020-2772-0","article-title":"Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion","volume":"588","author":"Benton","year":"2020","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"108630","DOI":"10.1016\/j.celrep.2020.108630","article-title":"D614G mutation alters SARS-CoV-2 Spike conformation and enhances protease cleavage at the S1\/S2 junction","volume":"34","author":"Gobeil","year":"2021","journal-title":"Cell Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1038\/s41467-022-32262-8","article-title":"SARS-CoV-2 variants of concern: Spike protein mutational analysis and epitope for broad neutralization","volume":"13","author":"Mannar","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Yang, T.J., Yu, P.Y., Chang, Y.C., and Hsu, S.T.D. (2021). Local refinement of SARS-CoV-2 S-Kappa variant (B.1.617.1) RBD and Angiotensin-converting enzyme 2 (ACE2) ectodomain. bioRxiv.","DOI":"10.2210\/pdb7v87\/pdb"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41467-022-28882-9","article-title":"Cryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain","volume":"13","author":"Ye","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41586-022-04980-y","article-title":"BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection","volume":"608","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1016\/j.cell.2021.02.033","article-title":"Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera","volume":"184","author":"Supasa","year":"2021","journal-title":"Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.cell.2022.06.005","article-title":"Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum","volume":"185","author":"Tuekprakhon","year":"2022","journal-title":"Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41594-020-00549-3","article-title":"A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent","volume":"28","author":"Xiao","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41422-022-00672-4","article-title":"Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins","volume":"32","author":"Xu","year":"2022","journal-title":"Cell Res."},{"key":"ref_120","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":"ref_121","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1016\/j.cell.2022.05.014","article-title":"Potent cross-reactive antibodies following Omicron breakthrough in vaccinees","volume":"185","author":"Nutalai","year":"2022","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nsb1203-980","article-title":"Announcing the worldwide Protein Data Bank","volume":"10","author":"Berman","year":"2003","journal-title":"Nature Struct. Mol. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0022-2836(77)80200-3","article-title":"The Protein Data Bank: A computer-based archival file for macromolecular structures","volume":"112","author":"Bernstein","year":"1977","journal-title":"J. Mol. Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1021\/ct900587b","article-title":"Prediction of absolute solvation free energies using Molecular Dynamics free energy perturbation and the OPLS force field","volume":"6","author":"Shivakumar","year":"2010","journal-title":"J. Chem. Theory Comput."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all-atom protein loop prediction","volume":"55","author":"Jacobson","year":"2004","journal-title":"Proteins"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0022-2836(02)00470-9","article-title":"On the role of the crystal environment in determining protein side-chain conformations","volume":"320","author":"Jacobson","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1747-0285.2007.00483.x","article-title":"New method for fast and accurate binding-site identification and analysis","volume":"69","author":"Halgren","year":"2007","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1021\/ci800324m","article-title":"Identifying and characterizing binding sites and assessing druggability","volume":"49","author":"Halgren","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide:\u2009 A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1016\/j.bmc.2005.12.032","article-title":"New insights about HERG blockade obtained from protein modeling, potential energy mapping, and docking studies","volume":"14","author":"Farid","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced fit effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1747-0285.2005.00327.x","article-title":"Use of an induced fit receptor structure in virtual screening","volume":"67","author":"Sherman","year":"2006","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_138","first-page":"764","article-title":"Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I","volume":"21","author":"Geromichalos","year":"2016","journal-title":"J. BUON"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.physchem.51.1.129","article-title":"Generalized born models of macromolecular solvation effects","volume":"51","author":"Bashford","year":"2000","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref_140","unstructured":"DeLano, W.L. (2006). The PyMol Molecular Graphics System 0.99, DeLano Scientific."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/21\/7572\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:10:45Z","timestamp":1760145045000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/21\/7572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,4]]},"references-count":140,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["molecules27217572"],"URL":"https:\/\/doi.org\/10.3390\/molecules27217572","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,4]]}}}