{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:23:59Z","timestamp":1790868239231,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008413","name":"Instrumentariumin Tiedes\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008413","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"DOI":"10.3389\/fchem.2020.589769","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T02:57:43Z","timestamp":1605754663000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Screening of Natural Products Targeting SARS-CoV-2\u2013ACE2 Receptor Interface \u2013 A MixMD Based HTVS Pipeline"],"prefix":"10.3389","volume":"8","author":[{"given":"Krishnasamy","family":"Gopinath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmeri M.","family":"Jokinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami T.","family":"Kurkinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli T.","family":"Pentik\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14214","DOI":"10.1038\/s41598-020-71188-3","article-title":"Dynamics of the ACE2\u2013SARS-CoV-2\/SARS-CoV spike protein interface reveal unique mechanisms","volume":"10","author":"Ali","year":"2020","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s10822-007-9159-2","article-title":"An improved relaxed complex scheme for receptor flexibility in computer-aided drug design","volume":"22","author":"Amaro","year":"2008","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1016\/j.bpj.2018.02.038","article-title":"Ensemble docking in drug discovery","volume":"114","author":"Amaro","year":"2018","journal-title":"Biophys. J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1063\/1.439486","article-title":"Molecular dynamics simulations at constant pressure and\/or temperature","volume":"72","author":"Andersen","year":"1980","journal-title":"J. Chem. Phys."},{"key":"B5","doi-asserted-by":"publisher","first-page":"23379","DOI":"10.1039\/D0RA03774E","article-title":"Natural products' role against COVID-19","volume":"10","author":"Antonio","year":"2020","journal-title":"RSC Adv."},{"key":"B6","doi-asserted-by":"publisher","first-page":"D935","DOI":"10.1093\/nar\/gku886","article-title":"Super natural II-a database of natural products","volume":"43","author":"Banerjee","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e0119771","DOI":"10.1371\/journal.pone.0119771","article-title":"Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies","volume":"10","author":"Bhutani","year":"2015","journal-title":"PLoS ONE"},{"key":"B8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1145\/1188455.1188544","article-title":"Scalable algorithms for molecular dynamics simulations on commodity clusters","volume-title":"Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing - SC '06","author":"Bowers","year":"2006"},{"key":"B9","doi-asserted-by":"publisher","first-page":"497","DOI":"10.3390\/v12050497","article-title":"The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor","volume":"12","author":"Brielle","year":"2020","journal-title":"Viruses"},{"key":"B10","unstructured":"CaseD. A.\n            BelfonK.\n            Ben-ShalomI. Y.\n            BrozellS. R.\n            CeruttiD. S.\n            IIIT. E. C.\n          31909743San Fransisco, CAUniversity of California, San FransiscoAMBER 2020.2020"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/2020.06.25.170639","article-title":"The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening","author":"Chen","year":"2020","journal-title":"bioRxiv [Preprint]"},{"key":"B12","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh ewald: an N\u00b7log(N) method for ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1761881","article-title":"Natural products may interfere with SARS-CoV-2 attachment to the host cell","author":"Elfiky","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B14","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"B15","doi-asserted-by":"publisher","first-page":"5152","DOI":"10.1038\/ncomms6152","article-title":"On the absence of intrahelical DNA dynamics on the \u03bcs to ms timescale","volume":"5","author":"Galindo-Murillo","year":"2014","journal-title":"Nat. Commun."},{"key":"B16","doi-asserted-by":"publisher","first-page":"8685","DOI":"10.1021\/acs.jpcb.6b03515","article-title":"Moving beyond active-site detection: MixMD applied to allosteric systems","volume":"120","author":"Ghanakota","year":"2016","journal-title":"J. Phys. Chem. B"},{"key":"B17","doi-asserted-by":"publisher","first-page":"168","DOI":"10.2174\/2210315508666180622113414","article-title":"Isolation of natural compounds from syzygium densiflorum fruits and exploring its chemical property, therapeutic role in diabetic management","volume":"10","author":"Gopinath","year":"2020","journal-title":"Nat. Prod. J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1021\/ct200909j","article-title":"Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. generalized born","volume":"8","author":"G\u00f6tz","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"B19","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1529\/biophysj.107.120501","article-title":"Molecular dynamics and principal components analysis of human telomeric quadruplex multimers","volume":"95","author":"Haider","year":"2008","journal-title":"Biophys. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.26434\/chemrxiv.12652832","article-title":"Computational drug repurposing studies on the ACE2-spike (RBD) interface of SARS-CoV-2","author":"Jani","year":"2020","journal-title":"ChemRXiv [Preprint]"},{"key":"B21","unstructured":"Fragment- and negative image-based screening of phosphodiesterase 10A inhibitors17991812\n            JokinenE. M.\n            PostilaP. A.\n            AhinkoM.\n            NiinivehmasS.\n            Pentik\u00e4inenO. T.\n          10.1111\/cbdd.1358431260165Chem. Biol. Drug Des.942019"},{"key":"B22","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1780947","article-title":"Natural compounds from Clerodendrum spp. as possible therapeutic candidates against SARS-CoV-2: an in silico investigation","author":"Kar","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B24","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/jcc.20820","article-title":"GLYCAM06: a generalizable biomolecular force field","volume":"29","author":"Kirschner","year":"2008","journal-title":"Carbohydrates. J. Comput. Chem."},{"key":"B25","unstructured":"Can honey, omega-3, resistant potato starch help fight COVID-19? Researchers to examine via clinical trials\n            KoeT.\n          News & Analysis on Supplements, Health and Nutrition \u2013 Asia Pacific"},{"key":"B26","unstructured":"COVID-19 natural product trial: New curcumin, artemisinin supplement to be tested on patients\n            KoeT.\n          News & Analysis on Supplements, Health and Nutrition \u2013 Asia Pacific"},{"key":"B27","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1021\/ci800298z","article-title":"Empirical scoring functions for advanced protein-ligand docking with PLANTS","volume":"49","author":"Korb","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"B28","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.1021\/acs.jcim.9b00383","article-title":"Getting docking into shape using negative image-based rescoring","volume":"59","author":"Kurkinen","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"B30","doi-asserted-by":"publisher","first-page":"260","DOI":"10.3389\/fphar.2018.00260","article-title":"Improving docking performance using negative image-based rescoring","volume":"9","author":"Kurkinen","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"104445","DOI":"10.1016\/j.meegid.2020.104445","article-title":"Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission","volume":"85","author":"Laha","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"B32","doi-asserted-by":"publisher","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":"B33","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1021\/ci400741u","article-title":"Parameter choice matters: validating probe parameters for use in mixed-solvent simulations","volume":"54","author":"Lexa","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"B34","unstructured":"TCM and COVID-19: China conducting trials to test efficacy and safety of traditional herbal interventions\n            LimG. Y.\n          News & Analysis on Supplements, Health and Nutrition \u2013 Asia Pacific2020"},{"key":"B35","doi-asserted-by":"publisher","first-page":"198082","DOI":"10.1016\/j.virusres.2020.198082","article-title":"Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2","volume":"288","author":"Lin","year":"2020","journal-title":"Virus Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.joim.2020.02.004","article-title":"Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2)","volume":"18","author":"Ling","year":"2020","journal-title":"J. Integr. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.biochi.2020.05.012","article-title":"SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention","volume":"175","author":"Mahmoud","year":"2020","journal-title":"Biochimie"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py : an efficient program for end-state free energy calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e1008762","DOI":"10.1371\/journal.ppat.1008762","article-title":"COVID-19 pandemic: insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2","volume":"16","author":"Mittal","year":"2020","journal-title":"PLoS Pathog."},{"key":"B41","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1007\/s10822-015-9870-3","article-title":"Ultrafast protein structure-based virtual screening with panther","volume":"29","author":"Niinivehmas","year":"2015","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"B42","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0065-3233(03)66002-X","article-title":"Force fields for protein simulations","volume":"66","author":"Ponder","year":"2003","journal-title":"Advances"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"B44","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkenes","volume":"23","author":"Ryckaert","year":"1976","journal-title":"J. Comp. Phys."},{"key":"B45","doi-asserted-by":"publisher","first-page":"923","DOI":"10.3389\/fphar.2018.00923","article-title":"Bridging molecular docking to molecular dynamics in exploring ligand-protein recognition process: an overview","volume":"9","author":"Salmaso","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1021\/ct400314y","article-title":"Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. explicit solvent particle mesh ewald","volume":"9","author":"Salomon-Ferrer","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"B47","doi-asserted-by":"publisher","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B48","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jare.2020.03.005","article-title":"COVID-19 infection: origin, transmission, and characteristics of human coronaviruses","volume":"24","author":"Shereen","year":"2020","journal-title":"J. Adv. Res."},{"key":"B49","unstructured":"SteeleJ.\n          Lab Finds 125 Naturally Occurring Compounds with Potential Against COVID-19. 1\u201332020"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1101\/2020.02.16.951723","article-title":"SARS-CoV-2 and SARS-CoV spike-RBD structure and receptor binding comparison and potential implications on neutralizing antibody and vaccine development","author":"Sun","year":"2020","journal-title":"bioRXiv [Preprint]"},{"key":"B51","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/bip.22742","article-title":"Identifying binding hot spots on protein surfaces by mixed-solvent molecular dynamics: HIV-1 protease as a test case","volume":"105","author":"Ung","year":"2016","journal-title":"Biopolymers"},{"key":"B52","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1021\/ci800315d","article-title":"ShaEP: molecular overlay based on shape and electrostatic potential","volume":"49","author":"Vainio","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1762743","article-title":"Stilbene-based natural compounds as promising drug candidates against COVID-19","author":"Wahedi","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B54","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","author":"Walls","year":"2020","journal-title":"Cell 181"},{"key":"B55","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic atom type and bond type perception in molecular mechanical calculations","volume":"25","author":"Wang","year":"2006","journal-title":"J. Mol. Graph. Model."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"B57","unstructured":"BrazzavilleWorld Health Organization\u2013 Regional Office for AfricaWHO Supports Scientifically-Proven Traditional Medicine2020"},{"key":"B58","doi-asserted-by":"publisher","first-page":"acs.jmedchem.0c00502","DOI":"10.1021\/acs.jmedchem.0c00502","article-title":"Inhibitors of SARS-CoV-2 entry: current and future opportunities","volume":"15","author":"Xiu","year":"2020","journal-title":"J. Med. Chem."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.7150\/ijbs.45538","article-title":"Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective","volume":"16","author":"Yang","year":"2020","journal-title":"Int. J. Biol. Sci."}],"container-title":["Frontiers in Chemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2020.589769\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T02:58:22Z","timestamp":1605754702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2020.589769\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":59,"alternative-id":["10.3389\/fchem.2020.589769"],"URL":"https:\/\/doi.org\/10.3389\/fchem.2020.589769","relation":{},"ISSN":["2296-2646"],"issn-type":[{"value":"2296-2646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,19]]},"article-number":"589769"}}