Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches
Hourieh Kalhor, Solmaz Sadeghi, Hoda Abolhasani, Reyhaneh Kalhor, Hamzeh Rahimi
Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1824816
Most recently, the new coronavirus (SARS-CoV-2) has been recognized as a pandemic by the World Health Organization (WHO) while this virus shares substantial similarity with SARS-CoV. So far, no definitive vaccine or drug has been developed to cure Covid-19 disease, since many important aspects about Covid-19 such as pathogenesis and proliferation pathways are still unclear. It was proven that human ACE2 is the main receptor for the entry of Covid-19 into lower respiratory tract epithelial cells through interaction with SARS-CoV-2 S protein. Based on this observation, it is expected that the virus infection can be inhibited if protein-protein interaction is prevented. In this study, using structurebased virtual screening of FDA databases, several lead drugs were discovered based on the ACE2binding pocket of SARS-CoV-2 S protein. Then, binding affinity, binding modes, critical interactions, and pharmaceutical properties of the lead drugs were evaluated. Among the previously approved drugs, Diammonium Glycyrrhizinate, Digitoxin, Ivermectin, Rapamycin, Rifaximin, and Amphotericin B represented the most desirable features, and can be possible candidates for Covid-19 therapies. Furthermore, molecular dynamics (MD) simulation was accomplished for three S protein/drug complexes with the highest binding affinity and best conformation and binding free energies were also computed with the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Results demonstrated the stable binding of these compounds to the S protein; however, in order to confirm the curative effect of these drugs, clinical trials must be done.
References
Abraham, Murtola, Schulz, Smith, Hess et al., GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX,
doi:10.1016/j.softx.2015.06.001Agostini, Andres, Sims, Graham, Sheahan et al., Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease, mBio,
doi:10.1128/mBio.00221-18Alobid, Bernal, Calvo, Vilaseca, Berenguer et al., Treatment of rhinocerebral mucormycosis by combination of endoscopic sinus debridement and amphotericin B, American Journal of Rhinology,
doi:10.1177/1945892401Amarelle, Lecuona, The antiviral effects of Na, K-ATPase inhibition: A minireview, International Journal of Molecular Sciences,
doi:10.3390/ijms19082154Athanasios, Psychos, Domenikos, Communication: Novel drug combination Doxycycline-Melatonin-Digoxin (D-M-D) for possible Covid-19 treatment, Journal of Modern Medicinal Chemistry,
doi:10.12970/2308-8044.2020.08.01Bussi, Donadio, Parrinello, Canonical sampling through velocity rescaling, The Journal of Chemical Physics,
doi:10.1063/1.2408420Chang, Tung, Lee, Chen, Hsiao et al., Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking, Preprints,
doi:10.20944/preprints202002.0242.v2Cinatl, Morgenstern, Bauer, Chandra, Rabenau et al., Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus, The Lancet,
doi:10.1016/S0140-6736(03)13615-XDarden, York, Pedersen, Particle mesh Ewald: An NÁ log (N) method for Ewald sums in large systems, The Journal of Chemical Physics,
doi:10.1063/1.464397De Oliveira, Rocha, Paluch, Costa, Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening, Journal of Biomolecular Structure and Dynamics,
doi:10.1080/07391102.2020.1772885Delano, Pymol: An open-source molecular graphics tool, CCP4 Newsletter on Protein Crystallography
Elfiky, Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study, Life Sciences,
doi:10.1016/j.lfs.2020.117592Feng, Wang, Yao, Zhang, Tian, Diammonium glycyrrhizinate, a component of traditional Chinese medicine Gan-Cao, prevents murine T-cell-mediated fulminant hepatitis in IL-10-and IL-6dependent manners, International Immunopharmacology,
doi:10.1016/j.intimp.2007.05.011Gupta, Ammonium glycyrrhizinate: a compherensive review of its traditionaluse, phytochemistry, pharmacology & safety, Asian Journal of Pharmaceutical Education and Research
G€ Otz, Magar, Dornfeld, Giese, Pohlmann et al., Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Scientific Reports,
doi:10.1038/srep23138Hackett, Sylvester, Joss, Calvin, Synergistic effect of rifamycin derivatives and amphotericin B on viral transformation of a murine cell line, Proceedings of the National Academy of Sciences,
doi:10.1073/pnas.69.12.3653Hess, Bekker, Berendsen, Fraaije, Ito et al., Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV), Journal of Computational Chemistry,
doi:10.1016/0166-3542(88)90047-2Kalhor, Rahimi, Akbari Eidgahi, Teimoori-Toolabi, Novel small molecules against two binding sites of Wnt2 protein as potential drug candidates for colorectal cancer: A structure based virtual screening approach, Iranian Journal of Pharmaceutical Research,
doi:10.22037/IJPR.2019.15297.13037Kalhor, Sadeghi, Marashiyan, Kalhor, Aghaei Gharehbolagh et al., Identification of new DNA gyrase inhibitors based on bioactive compounds from streptomyces: Structure-based virtual screening and molecular dynamics simulations approaches, Journal of Biomolecular Structure & Dynamics,
doi:10.1080/07391102.2019.1588784Kandeel, Al-Nazawi, Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease, Life Sciences,
doi:10.1016/j.lfs.2020.117627Koes, Baumgartner, Camacho, Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise, Journal of Chemical Information and Modeling,
doi:10.1021/ci300604zKumari, Kumar, Consortium, Lynn, g_mmpbsaA A GROMACS tool for high-throughput MM-PBSA calculations, Journal of Chemical Information and Modeling,
doi:10.1021/ci500020mLaskowski, Swindells, LigPlotþ: Multiple ligand-protein interaction diagrams for drug discovery, ACS Publications,
doi:10.1021/ci200227uLi, Li, Farzan, Harrison, Structure of SARS coronavirus spike receptor-binding domain complexed with receptor, Science,
doi:10.1126/science.1116480Lipinski, Lombardo, Dominy, Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Advanced Drug Delivery Reviews,
doi:10.1016/S0169-409X(00)00129-0Lundberg, Pinkham, Baer, Amaya, Narayanan et al., Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication, Antiviral Research,
doi:10.1016/j.antiviral.2013.10.004Mohammadi, Kometiani, Xie, Askari, Role of protein kinase C in the signal pathways that link Naþ/Kþ-ATPase to ERK1/2, Journal of Biological Chemistry,
doi:10.1074/jbc.M107892200Morgenstern, Michaelis, Baer, Doerr, Cinatl, Ribavirin and interferon-b synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines, Biochemical and Biophysical Research Communications,
doi:10.1016/j.bbrc.2004.11.128Morris, Huey, Lindstrom, Sanner, Belew et al., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, Journal of Computational Chemistry,
doi:10.1002/jcc.21256Mukhtar, Mukhtar, Coronavirus (COVID-19): Let's prevent not panic, Journal of Ayub Medical College Abbottabad
Numazaki, Nagata, Sato, Chiba, Effect of glycyrrhizin, cyclosporin A, and tumor necrosis factor a on infection of U-937 and MRC-5 cells by human cytomegalovirus, Journal of Leukocyte Biology,
doi:10.1002/jlb.55.1.24O'boyle, Banck, James, Morley, Vandermeersch et al., Open Babel: An open chemical toolbox, Journal of Cheminformatics,
doi:10.1021/ci200227uParrinello, Rahman, Polymorphic transitions in single crystals: A new molecular dynamics method Polymorphic transitions in single crystals: A new molecular dynamics method, Journal of Applied Physics,
doi:10.1063/1.328693Pollard, Pollard, Pollard, Classical drug digitoxin inhibits influenza cytokine storm, with implications for COVID-19 therapy, bioRxiv,
doi:10.1101/2020.04.09.034983Rismanbaf, Potential treatments for COVID-19; a narrative literature review, Archives of Academic Emergency Medicine
Sander, Freyss, Von Korff, Rufener, DataWarrior: An open-source program for chemistry aware data visualization and analysis, Journal of Chemical Information and Modeling,
doi:10.1021/ci500588jSch€ Uttelkopf, Van Aalten, PRODRG: A tool for highthroughput crystallography of protein-ligand complexes, Acta Crystallographica Section D Biological Crystallography,
doi:10.1107/S0907444904011679Shanmugaraj, Malla, Phoolcharoen, Emergence of novel coronavirus 2019-nCoV: Need for rapid vaccine and biologics development, Pathogens,
doi:10.3390/pathogens9020148Shiri, Pirhadi, Ghasemi, Dynamic structure based pharmacophore modeling of the Acetylcholinesterase reveals several potential inhibitors, Journal of Biomolecular Structure & Dynamics,
doi:10.1080/07391102.2018.1468281Shiri, Pirhadi, Rahmani, Identification of new potential HIV-1 reverse transcriptase inhibitors by QSAR modeling and structure-based virtual screening, Journal of Receptor and Signal Transduction Research,
doi:10.1080/10799893.2017.1414844Song, Gui, Wang, Xiang, Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2, PLOS Pathogens,
doi:10.1371/journal.ppat.1007236Tay, Fraser, Chan, Moreland, Rathore et al., Nuclear ocalization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENVserotypes by the inhibitor Ivermectin, Antiviral Research,
doi:10.1016/j.antiviral.2013.06.002Thakur, Raj, Pharmacological perspective of Glycyrrhiza glabra Linn: A mini-review, Journal of Analytical & Pharmaceutical Research,
doi:10.15406/japlr.2017.05.00156Utsunomiya, Kobayashi, Herndon, Pollard, Suzuki et al., Glycyrrhizin(20b-carboxy-11-oxo-30-norolean-12-en-3b-yl-2-Ob-d-glucopyranuronosyl-a-d-glucopyranosiduronic acid) improves the resistance of thermally injured mice to opportunistic infection of herpes simplex virus type 1, Antimicrobial Agents and Chemotherapy,
doi:10.1128/AAC.41.3.551Van Tilbeurgh, Bezzine, Cambillau, Verger, Carriere, Colipase: Structure and interaction with pancreatic lipase, Biochimica et Biophysica Acta (Bba) -Molecular and Cell Biology of Lipids,
doi:10.1016/S1388-1981(99)00149-3Visualizer, Version 4.5 (software
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin a/b-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, The Biochemical Journal,
doi:10.1042/BJ20120150Wrapp, Wang, Corbett, Goldsmith, Hsieh et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science,
doi:10.1126/science.abb2507Xu, Chen, Wang, Feng, Zhou et al., Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission, Science China Life Sciences,
doi:10.1007/s11427-020-1637-5Zhou, Hou, Shen, Huang, Martin et al., Network-based drug repurposing for novel coronavirus 2019-nCoV/ SARS-CoV-2, Cell Discovery,
doi:10.1038/s41421-020-0153-3Zhu, Zhang, Wang, Li, Yang et al., A novel coronavirus from patients with pneumonia in China, 2019, The New England Journal of Medicine,
doi:10.1056/NEJMoa2001017{ 'indexed': {'date-parts': [[2024, 2, 20]], 'date-time': '2024-02-20T10:18:49Z', 'timestamp': 1708424329552},
'reference-count': 70,
'publisher': 'Informa UK Limited',
'issue': '3',
'content-domain': {'domain': ['www.tandfonline.com'], 'crossmark-restriction': True},
'published-print': {'date-parts': [[2022, 2, 11]]},
'DOI': '10.1080/07391102.2020.1824816',
'type': 'journal-article',
'created': {'date-parts': [[2020, 9, 24]], 'date-time': '2020-09-24T12:10:25Z', 'timestamp': 1600949425000},
'page': '1299-1315',
'update-policy': 'http://dx.doi.org/10.1080/tandf_crossmark_01',
'source': 'Crossref',
'is-referenced-by-count': 30,
'title': 'Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2\u2009S protein '
'and human ACE2 interaction through virtual screening approaches',
'prefix': '10.1080',
'volume': '40',
'author': [ { 'given': 'Hourieh',
'family': 'Kalhor',
'sequence': 'first',
'affiliation': [ { 'name': 'Cellular and Molecular Research Center, Qom University of '
'Medical Sciences, Qom, Iran'},
{ 'name': 'Molecular Medicine Department, Biotechnology Research Center, '
'Pasteur Institute of Iran, Tehran, Iran'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-5861-2606',
'authenticated-orcid': False,
'given': 'Solmaz',
'family': 'Sadeghi',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Medical Biotechnology, School of Advanced '
'Technologies in Medicine, Tehran University of Medical Sciences, '
'Tehran, Iran'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-9174-5304',
'authenticated-orcid': False,
'given': 'Hoda',
'family': 'Abolhasani',
'sequence': 'additional',
'affiliation': [ { 'name': 'Cellular and Molecular Research Center, Qom University of '
'Medical Sciences, Qom, Iran'},
{ 'name': 'Spiritual Health Research Center, Qom University of Medical '
'Sciences, Qom, Iran'},
{ 'name': 'Department of Pharmacology, School of Medicine, Qom University '
'of Medical Sciences, Qom, Iran'}]},
{ 'given': 'Reyhaneh',
'family': 'Kalhor',
'sequence': 'additional',
'affiliation': [ { 'name': 'Cellular and Molecular Research Center, Qom University of '
'Medical Sciences, Qom, Iran'},
{ 'name': 'Department of Genetics, Colleague of Sciences, Kazerun branch, '
'Islamic Azad University, Kazerun, Iran'}]},
{ 'given': 'Hamzeh',
'family': 'Rahimi',
'sequence': 'additional',
'affiliation': [ { 'name': 'Molecular Medicine Department, Biotechnology Research Center, '
'Pasteur Institute of Iran, Tehran, Iran'}]}],
'member': '301',
'published-online': {'date-parts': [[2020, 9, 24]]},
'reference': [ {'key': 'CIT0001', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.softx.2015.06.001'},
{'key': 'CIT0002', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/mBio.00221-18'},
{'key': 'CIT0003', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/194589240101500508'},
{'key': 'CIT0004', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/ijms19082154'},
{ 'key': 'CIT0005',
'doi-asserted-by': 'publisher',
'DOI': '10.1002/(SICI)1097-0142(19970415)79:8<1494::AID-CNCR8>3.0.CO;2-B'},
{'key': 'CIT0006', 'doi-asserted-by': 'publisher', 'DOI': '10.12970/2308-8044.2020.08.01'},
{'key': 'CIT0007', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/0166-3542(87)90025-8'},
{'key': 'CIT0008', 'doi-asserted-by': 'publisher', 'DOI': '10.1063/1.2408420'},
{'key': 'CIT0009', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2020.104787'},
{ 'key': 'CIT0010',
'doi-asserted-by': 'publisher',
'DOI': '10.20944/preprints202002.0242.v2'},
{'key': 'CIT0011', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(03)13615-X'},
{'key': 'CIT0012', 'doi-asserted-by': 'publisher', 'DOI': '10.1063/1.464397'},
{'key': 'CIT0013', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/07391102.2020.1772885'},
{ 'key': 'CIT0014',
'first-page': '82',
'volume': '40',
'author': 'DeLano W. L.',
'year': '2002',
'journal-title': 'CCP4 Newsletter on Protein Crystallography'},
{'key': 'CIT0015', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.lfs.2020.117477'},
{'key': 'CIT0016', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.lfs.2020.117592'},
{'key': 'CIT0017', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.intimp.2007.05.011'},
{'key': 'CIT0018', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/srep23138'},
{'key': 'CIT0019', 'doi-asserted-by': 'publisher', 'DOI': '10.1073/pnas.69.12.3653'},
{ 'key': 'CIT0020',
'doi-asserted-by': 'publisher',
'DOI': '10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H'},
{'key': 'CIT0021', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/0166-3542(88)90047-2'},
{'key': 'CIT0022', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41586-020-2223-y'},
{ 'issue': '2',
'key': 'CIT0023',
'volume': '19',
'author': 'Kalhor H.',
'year': '2020',
'journal-title': 'Iranian Journal of Pharmaceutical Research'},
{'key': 'CIT0024', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/07391102.2019.1588784'},
{'key': 'CIT0025', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.lfs.2020.117627'},
{'key': 'CIT0026', 'doi-asserted-by': 'publisher', 'DOI': '10.1021/ci300604z'},
{'key': 'CIT0027', 'doi-asserted-by': 'publisher', 'DOI': '10.1021/ci500020m'},
{'key': 'CIT0028', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/nar/gkn860'},
{ 'key': 'CIT0029',
'volume-title': 'LigPlot+: Multiple ligand–protein interaction diagrams for drug '
'discovery',
'author': 'Laskowski R. A.',
'year': '2011'},
{'key': 'CIT0030', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cmet.2014.01.001'},
{'key': 'CIT0031', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.1116480'},
{'key': 'CIT0032', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0166-3542(03)00030-5'},
{'key': 'CIT0033', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.addr.2012.09.019'},
{'key': 'CIT0034', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2013.10.004'},
{'key': 'CIT0035', 'doi-asserted-by': 'publisher', 'DOI': '10.1074/jbc.M107892200'},
{'key': 'CIT0036', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.bbrc.2004.11.128'},
{'key': 'CIT0037', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/jcc.21256'},
{ 'issue': '1',
'key': 'CIT0038',
'first-page': '141',
'volume': '32',
'author': 'Mukhtar F.',
'year': '2020',
'journal-title': 'Journal of Ayub Medical College Abbottabad'},
{'key': 'CIT0039', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/jlb.55.1.24'},
{'key': 'CIT0040', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/1758-2946-3-33'},
{'key': 'CIT0041', 'doi-asserted-by': 'publisher', 'DOI': '10.1063/1.328693'},
{'key': 'CIT0042', 'author': 'Pollard H. B.', 'year': '2020', 'journal-title': 'bioRxiv'},
{ 'issue': '1',
'key': 'CIT0043',
'volume': '8',
'author': 'Rismanbaf A.',
'year': '2020',
'journal-title': 'Archives of Academic Emergency Medicine'},
{'key': 'CIT0044', 'doi-asserted-by': 'publisher', 'DOI': '10.2533/chimia.2007.312'},
{'key': 'CIT0045', 'doi-asserted-by': 'publisher', 'DOI': '10.1021/ci500588j'},
{'key': 'CIT0046', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/0166-3542(96)00942-4'},
{'key': 'CIT0047', 'doi-asserted-by': 'publisher', 'DOI': '10.1107/S0907444904011679'},
{ 'key': 'CIT0048',
'doi-asserted-by': 'crossref',
'unstructured': 'Sekhar, T. (2020). Virtual screening based prediction of potential drugs '
'for COVID-19. Preprints.org. '
'https://doi.org/10.20944/preprints202002.0418.v2',
'DOI': '10.20944/preprints202002.0418.v2'},
{'key': 'CIT0049', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41586-020-2179-y'},
{'key': 'CIT0050', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/pathogens9020148'},
{'key': 'CIT0051', 'doi-asserted-by': 'publisher', 'DOI': '10.3748/wjg.v22.i29.6638'},
{'key': 'CIT0052', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/07391102.2018.1468281'},
{'key': 'CIT0053', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/10799893.2017.1414844'},
{'key': 'CIT0054', 'doi-asserted-by': 'publisher', 'DOI': '10.1159/000149390'},
{'key': 'CIT0055', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.ppat.1007236'},
{'key': 'CIT0056', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/gutjnl-2014-308971'},
{'key': 'CIT0057', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2013.06.002'},
{'key': 'CIT0058', 'doi-asserted-by': 'publisher', 'DOI': '10.15406/japlr.2017.05.00156'},
{ 'issue': '1',
'key': 'CIT0059',
'first-page': '58',
'volume': '7',
'author': 'Tinku Gupta M. M.',
'year': '2018',
'journal-title': 'Asian Journal of Pharmaceutical Education and Research'},
{'key': 'CIT0060', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/0165-2478(94)00183-R'},
{'key': 'CIT0061', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/AAC.41.3.551'},
{'key': 'CIT0062', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S1388-1981(99)00149-3'},
{ 'key': 'CIT0063',
'unstructured': 'Visualizer, B. D. S. (2017). Version 4.5 (software). '
'http://mayavi.sourceforge.net'},
{'key': 'CIT0064', 'doi-asserted-by': 'publisher', 'DOI': '10.1042/BJ20120150'},
{'key': 'CIT0065', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.abb2507'},
{'key': 'CIT0066', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41586-020-2008-3'},
{'key': 'CIT0067', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s11427-020-1637-5'},
{'key': 'CIT0068', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/molecules18066230'},
{'key': 'CIT0069', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41421-020-0153-3'},
{'key': 'CIT0070', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2001017'}],
'container-title': 'Journal of Biomolecular Structure and Dynamics',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.tandfonline.com/doi/pdf/10.1080/07391102.2020.1824816',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 1, 31]],
'date-time': '2022-01-31T13:12:23Z',
'timestamp': 1643634743000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1824816'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 9, 24]]},
'references-count': 70,
'journal-issue': {'issue': '3', 'published-print': {'date-parts': [[2022, 2, 11]]}},
'alternative-id': ['10.1080/07391102.2020.1824816'],
'URL': 'http://dx.doi.org/10.1080/07391102.2020.1824816',
'relation': {},
'ISSN': ['0739-1102', '1538-0254'],
'subject': ['Molecular Biology', 'General Medicine', 'Structural Biology'],
'container-title-short': 'Journal of Biomolecular Structure and Dynamics',
'published': {'date-parts': [[2020, 9, 24]]},
'assertion': [ { 'value': 'The publishing and review policy for this title is described in its Aims & '
'Scope.',
'order': 1,
'name': 'peerreview_statement',
'label': 'Peer Review Statement'},
{ 'value': 'http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tbsd20',
'URL': 'http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tbsd20',
'order': 2,
'name': 'aims_and_scope_url',
'label': 'Aim & Scope'},
{ 'value': '2020-08-01',
'order': 0,
'name': 'received',
'label': 'Received',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2020-09-12',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2020-09-24',
'order': 3,
'name': 'published',
'label': 'Published',
'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
