{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:58:20Z","timestamp":1780513100914,"version":"3.54.1"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONACyT","award":["749523\/857743"],"award-info":[{"award-number":["749523\/857743"]}]},{"name":"Direcci\u00f3n General de C\u00f3mputo y de Tecnolog\u00edas de Informaci\u00f3n","award":["LANCAD-UNAM-DGTIC-306"],"award-info":[{"award-number":["LANCAD-UNAM-DGTIC-306"]}]},{"name":"CONACyT","award":["A1-S-8866"],"award-info":[{"award-number":["A1-S-8866"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>CC Chemokine receptor 5 (CCR5), a member of the Superfamily of G Protein-Coupled Receptors (GPCRs), is an important effector in multiple physiopathological processes such as inflammatory and infectious entities, including central nervous system neuroinflammatory diseases such as Alzheimer\u2019s disease, recovery from nervous injuries, and in the HIV-AIDS infective processes. Thus, CCR5 is an attractive target for pharmacological modulation. Since maraviroc was described as a CCR5 ligand that modifies the HIV-AIDS progression, multiple efforts have been developed to describe the functionality of the receptor. In this work, we characterized key structural features of the CCR5 receptor employing extensive atomistic molecular dynamics (MD) in its apo form and in complex with an endogenous agonist, the chemokine CCL5\/RANTES, an HIV entry inhibitor, the partial inverse agonist maraviroc, and the experimental antagonists Compound 21 and 34, aiming to elucidate the structural features and mechanistic processes that constitute its functional states, contributing with structural details and a general understanding of this relevant system.<\/jats:p>","DOI":"10.1371\/journal.pone.0275269","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T17:32:56Z","timestamp":1666027976000},"page":"e0275269","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-3154","authenticated-orcid":true,"given":"Guillermo","family":"Goode-Romero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"pone.0275269.ref001","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJM199802123380706","article-title":"Chemokines\u2013Chemotactic cytokines that mediate inflammation","volume":"338","author":"AD Luster","year":"1998","journal-title":"N Engl J Med"},{"key":"pone.0275269.ref002","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1001\/jama.296.7.815","article-title":"Biology of CCR5 and Its Role in HIV Infection and Treatment","volume":"296","author":"MM Lederman","year":"2006","journal-title":"JAMA"},{"key":"pone.0275269.ref003","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0092-8674(00)80110-5","article-title":"Homozygous Defect in HIV-1 Coreceptor Accounts for Resistance of Some Multiply-Exposed Individuals to HIV-1 Infection","volume":"86","author":"R Liu","year":"1996","journal-title":"Cell"},{"key":"pone.0275269.ref004","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1357-2725(03)00172-9","article-title":"The chemokine receptor, CCR5","volume":"36","author":"A Mueller","year":"2004","journal-title":"Int J Biochem Cell Biol"},{"key":"pone.0275269.ref005","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.4049\/jimmunol.0990015","article-title":"The Unexpected Pleiotropic Activities of RANTES","volume":"182","author":"JA Levy","year":"2009","journal-title":"J Immunol"},{"key":"pone.0275269.ref006","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.2165\/00003495-200565130-00002","article-title":"Emerging Drug Targets for Antiretroviral Therapy","volume":"65","author":"JD Reeves","year":"2005","journal-title":"Drugs"},{"key":"pone.0275269.ref007","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1747-0285.2005.00319.x","article-title":"Peptide, Peptidomimetic and Small-molecule Drug Discovery Targeting HIV-1 Host-cell Attachment and Entry through gp120, gp41, CCR5 and CXCR4\u2020","volume":"67","author":"WM Kazmierski","year":"2006","journal-title":"Chem Biol Drug Des"},{"key":"pone.0275269.ref008","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1016\/S0968-0896(03)00161-5","article-title":"Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors","volume":"11","author":"W Kazmierski","year":"2003","journal-title":"Bioorg Med Chem"},{"issue":"80-","key":"pone.0275269.ref009","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1126\/science.1241475","article-title":"Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex","volume":"341","author":"Q Tan","year":"2013","journal-title":"Science"},{"key":"pone.0275269.ref010","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.cell.2019.01.044","article-title":"CCR5 is a therapeutic target for recovery after stroke and traumatic brain injury","volume":"176","author":"MT Joy","year":"2019","journal-title":"Cell"},{"key":"pone.0275269.ref011","doi-asserted-by":"crossref","first-page":"15382","DOI":"10.18632\/oncotarget.8097","article-title":"CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL\/6 mice","volume":"7","author":"GS Mi","year":"2016","journal-title":"Oncotarget"},{"key":"pone.0275269.ref012","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s10753-014-0014-z","article-title":"CCR5 blockade promotes M2 macrophage activation and improves locomotor recovery after spinal cord injury in mice","volume":"38","author":"F Li","year":"2015","journal-title":"Inflammation"},{"key":"pone.0275269.ref013","doi-asserted-by":"crossref","first-page":"815","DOI":"10.2174\/18715273113126660173","article-title":"Relation Between the Chemokine Receptor CCR5 and Microglia in Neurological Disorders: Consequences of Targeting CCR5 on Neuroinflammation, Neuronal Death and Regeneration in a Model of Epilepsy","volume":"12","author":"JP Louboutin","year":"2013","journal-title":"CNS Neurol Disord\u2014Drug Targets"},{"key":"pone.0275269.ref014","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1158\/0008-5472.CAN-19-1167","article-title":"Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology","volume":"79","author":"X Jiao","year":"2019","journal-title":"Cancer Res"},{"key":"pone.0275269.ref015","doi-asserted-by":"crossref","DOI":"10.21037\/tcr.2016.06.36","article-title":"CCR5 antagonist, an ally to fight against metastatic colorectal cancer","volume":"5","author":"N. Mukaida","year":"2016","journal-title":"Transl Cancer Res"},{"key":"pone.0275269.ref016","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1016\/j.bmcl.2010.06.003","article-title":"Anibamine, a natural product CCR5 antagonist, as a novel lead for the development of anti-prostate cancer agents","volume":"20","author":"X Zhang","year":"2010","journal-title":"Bioorg Med Chem Lett"},{"key":"pone.0275269.ref017","article-title":"Disruption of the CCL5\/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19","author":"BK Patterson","year":"2020","journal-title":"medRxiv: the preprint server for health sciences"},{"key":"pone.0275269.ref018","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nrn2977","article-title":"The role of G protein-coupled receptors in the pathology of Alzheimer\u2019s disease","volume":"12","author":"A Thathiah","year":"2011","journal-title":"Nat Rev Neurosci"},{"key":"pone.0275269.ref019","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.cyto.2010.10.008","article-title":"Depletion of CXCR2 inhibits \u03b3-secretase activity and amyloid-\u03b2 production in a murine model of Alzheimer\u2019s disease","volume":"53","author":"P Bakshi","year":"2011","journal-title":"Cytokine"},{"key":"pone.0275269.ref020","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1021\/cb800167a","article-title":"Novel Role of CXCR2 in Regulation of \u03b3-Secretase Activity","volume":"3","author":"P Bakshi","year":"2008","journal-title":"ACS Chem Biol"},{"key":"pone.0275269.ref021","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.3389\/fimmu.2019.02780","article-title":"Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal \u03b2-Amyloid Clearance Pathways and Slows Progression of Alzheimer\u2019s Like-Disease in PS1-APP Mice","volume":"10","author":"SE Hickman","year":"2019","journal-title":"Front Immunol"},{"key":"pone.0275269.ref022","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-017-0200-1","article-title":"Absence of CX3CR1 impairs the internalization of Tau by microglia","volume":"12","author":"M Bol\u00f3s","year":"2017","journal-title":"Mol Neurodegener"},{"key":"pone.0275269.ref023","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1073\/pnas.1316510111","article-title":"Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic-relapsing rat model for multiple sclerosis","volume":"111","author":"A Ridderstad Wollberg","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0275269.ref024","article-title":"Association of the CX3CR1 -V249I Variant with Neurofibrillary Pathology Progression in Late-Onset Alzheimer \u2018 s Disease","author":"A L\u00f3pez-L\u00f3pez","year":"2017","journal-title":"Mol Neurobiol"},{"key":"pone.0275269.ref025","first-page":"1373","article-title":"A novel CX3CR1 inhibitor AZD8797 facilitates early recovery of rat acute spinal cord injury by inhibiting inflammation and apoptosis","volume":"45","author":"C Guozhao","year":"2020","journal-title":"Int J Mol Med"},{"key":"pone.0275269.ref026","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.bbi.2020.10.021","article-title":"Analysis of CX3CR1 haplodeficiency in male and female APP(swe)\/PSEN1(dE9) mice along Alzheimer disease progression","volume":"91","author":"A-L Hemonnot-Girard","year":"2021","journal-title":"Brain Behav Immun"},{"key":"pone.0275269.ref027","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1523\/JNEUROSCI.2841-16.2017","article-title":"Deletion of the fractalkine receptor, CX3CR1, improves endogenous repair, axon sprouting and synaptogenesis after spinal cord injury in mice","volume":"37","author":"CM Freria","year":"2017","journal-title":"J Neurosci"},{"key":"pone.0275269.ref028","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.1074\/jbc.M110.168955","article-title":"New Insights into the Mechanisms whereby Low Molecular Weight CCR5 Ligands Inhibit HIV-1 Infection *","volume":"286","author":"J Garcia-Perez","year":"2011","journal-title":"J Biol Chem"},{"key":"pone.0275269.ref029","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.immuni.2017.05.002","article-title":"Structure of CC chemokine receptor 5 with a potent chemokine antagonist reveals mechanisms of chemokine recognition and molecular mimicry by HIV","volume":"46","author":"Y Zheng","year":"2017","journal-title":"Immunity"},{"key":"pone.0275269.ref030","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1093\/nar\/gky092","article-title":"UniProt: the universal protein knowledgebase","volume":"46","author":"T. UniProt Consortium","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pone.0275269.ref031","doi-asserted-by":"crossref","first-page":"9621","DOI":"10.1021\/acs.jmedchem.8b01077","article-title":"Structure-based design of 1-heteroaryl-1,3-propanediamine derivatives as a novel series of CC-chemokine receptor 5 antagonists","volume":"61","author":"P Peng","year":"2018","journal-title":"J Med Chem"},{"key":"pone.0275269.ref032","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/bph.12455","article-title":"The structural role of receptor tyrosine sulfation in chemokine recognition","volume":"171","author":"JP Ludeman","year":"2014","journal-title":"Br J Pharmacol"},{"key":"pone.0275269.ref033","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1111\/febs.14460","article-title":"The solution structure of monomeric CCL5 in complex with a doubly sulfated N-terminal segment of CCR5","volume":"285","author":"M Abayev","year":"2018","journal-title":"FEBS J"},{"key":"pone.0275269.ref034","first-page":"eabg8685","article-title":"Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist","volume":"7","author":"I Polina","year":"2022","journal-title":"Sci Adv"},{"key":"pone.0275269.ref035","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/1756-0500-5-367","article-title":"ACPYPE\u2014AnteChamber PYthon Parser interfacE","volume":"5","author":"AW Sousa da Silva","year":"2012","journal-title":"BMC Res Notes"},{"key":"pone.0275269.ref036","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/bioinformatics\/btk023","article-title":"OPM: Orientations of Proteins in Membranes database","volume":"22","author":"MA Lomize","year":"2006","journal-title":"Bioinformatics"},{"key":"pone.0275269.ref037","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: A Web-Based Graphical User Interface for CHARMM","volume":"29","author":"S Jo","year":"2008","journal-title":"J Comput Chem"},{"key":"pone.0275269.ref038","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/acs.jctc.5b00935","article-title":"CHARMM-GUI Input generator for NAMD, GROMACS, AMBER, OpenMM and CHARMM\/OpenMM simulations using the CHARMM36 additive force field","volume":"12","author":"J Lee","year":"2016","journal-title":"J Chem Theory Comput"},{"key":"pone.0275269.ref039","article-title":"Gromacs 5.0.7","author":"M Abraham","year":"2015"},{"key":"pone.0275269.ref040","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1021\/ct700200b","article-title":"P-LINCS:\u2009 A Parallel Linear Constraint Solver for Molecular Simulation","volume":"4","author":"B. Hess","year":"2008","journal-title":"J Chem Theory Comput"},{"key":"pone.0275269.ref041","doi-asserted-by":"crossref","first-page":"14101","DOI":"10.1063\/1.2408420","article-title":"Canonical sampling through velocity rescaling","volume":"126","author":"G Bussi","year":"2007","journal-title":"J Chem Phys"},{"key":"pone.0275269.ref042","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: A new molecular dynamics method","volume":"52","author":"M Parrinello","year":"1981","journal-title":"J Appl Phys"},{"key":"pone.0275269.ref043","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.2174\/092986712799320556","article-title":"Action of Molecular Switches in GPCRs\u2014Theoretical and Experimental Studies","volume":"19","author":"B Trzaskowski","year":"2010","journal-title":"Curr Med Chem"},{"key":"pone.0275269.ref044","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-94-007-7423-0_1","volume-title":"G Protein-Coupled Receptors\u2014Modeling and Simulation","author":"S Constanzi","year":"2014"},{"key":"pone.0275269.ref045","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"J-P Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"key":"pone.0275269.ref046","doi-asserted-by":"crossref","first-page":"11919","DOI":"10.1063\/1.1755656","article-title":"Accelerated molecular dynamics: A promising and efficient simulation method for biomolecules","volume":"120","author":"D Hamelberg","year":"2004","journal-title":"J Chem Phys"},{"key":"pone.0275269.ref047","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1021\/ct500090q","article-title":"Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation","volume":"10","author":"Y Miao","year":"2014","journal-title":"J Chem Theory Comput"},{"key":"pone.0275269.ref048","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1021\/acs.jctc.5b00436","article-title":"Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation","volume":"11","author":"Y Miao","year":"2015","journal-title":"J Chem Theory Comput"},{"key":"pone.0275269.ref049","author":"D Case","year":"2018","journal-title":"Amber"},{"key":"pone.0275269.ref050","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12859-015-0545-9","article-title":"CHEXVIS: a tool for molecular channel extraction and visualization","volume":"16","author":"Masood T Bin","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"pone.0275269.ref051","doi-asserted-by":"crossref","first-page":"98","DOI":"10.25080\/Majora-629e541a-00e","article-title":"MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations","author":"R Gowers","year":"2016","journal-title":"Proc 15th Python Sci Conf"},{"key":"pone.0275269.ref052","first-page":"1","author":"R Core Team","year":"2006","journal-title":"R: A language and environment for statistical computing. Computing"},{"key":"pone.0275269.ref053","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1093\/bioinformatics\/bts357","article-title":"Bendix: intuitive helix geometry analysis and abstraction","volume":"28","author":"ACE Dahl","year":"2012","journal-title":"Bioinformatics"},{"key":"pone.0275269.ref054","author":"L. Schr\u00f6dinger","year":"2015","journal-title":"The PyMOL Molecular Graphics System, Version 1.7.2.1"},{"key":"pone.0275269.ref055","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD\u2014Visual Molecular Dynamics","volume":"14","author":"W Humphrey","year":"1996","journal-title":"J Mol Graph"},{"key":"pone.0275269.ref056","author":"M. Molecular Design Ltd","year":"1993","journal-title":"ISIS\/Draw"},{"key":"pone.0275269.ref057","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/B978-0-12-417197-8.00008-0","article-title":"Receptor Conformation and Constitutive Activity in CCR5 Chemokine Receptor Fu and HIV Infection and Function","volume":"70","author":"CA Flanagan","year":"2014","journal-title":"Adv Pharmacol"},{"key":"pone.0275269.ref058","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1038\/s41467-021-24438-5","article-title":"Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5","volume":"12","author":"H Zhang","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0275269.ref059","article-title":"Investigation of Inhibition Mechanism of Chemokine Receptor CCR5 by Micro-second Molecular Dynamics Simulations","author":"R Ekhteiari Salmas","year":"2015","journal-title":"Sci Rep"},{"key":"pone.0275269.ref060","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1021\/acs.jmedchem.6b01309","article-title":"Structural Analysis of Chemokine Receptor-Ligand Interactions","volume":"60","author":"M Arimont","year":"2017","journal-title":"J Med Chem"},{"key":"pone.0275269.ref061","first-page":"366","volume-title":"Methods in Neurosciences","author":"JA Ballesteros","year":"1995"},{"key":"pone.0275269.ref062","doi-asserted-by":"crossref","first-page":"24332","DOI":"10.1039\/C4CP03331K","article-title":"Computational study on the interaction between CCR5 and HIV-1 entry inhibitor maraviroc: insight from accelerated molecular dynamics simulation and free energy calculation","volume":"16","author":"Q Bai","year":"2014","journal-title":"Phys Chem Chem Phys"},{"key":"pone.0275269.ref063","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1080\/07391102.2012.732342","article-title":"Computational modeling of human coreceptor CCR5 antagonist as a HIV-1 entry inhibitor: using an integrated homology modeling, docking, and membrane molecular dynamics simulation analysis approach","volume":"31","author":"CG Gadhe","year":"2013","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0275269.ref064","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1021\/ci050490k","article-title":"Modeling the Structural Basis of Human CCR5 Chemokine Receptor Function:\u2009 From Homology Model Building and Molecular Dynamics Validation to Agonist and Antagonist Docking","volume":"46","author":"A Fano","year":"2006","journal-title":"J Chem Inf Model"},{"key":"pone.0275269.ref065","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1084\/jem.176.2.587","article-title":"Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils","volume":"176","author":"Y Kameyoshi","year":"1992","journal-title":"J Exp Med"},{"key":"pone.0275269.ref066","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature08144","article-title":"The structure andfunction of G-protein coupled receptors","volume":"459","author":"DM Rosenbaum","year":"2009","journal-title":"Nature"},{"key":"pone.0275269.ref067","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms5733","article-title":"Activation of G-protein coupled receptors correlates with the formation of a continuous internal water pathway","volume":"5","author":"S Yuan","year":"2014","journal-title":"Nat Commun"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0275269","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T17:34:02Z","timestamp":1666028042000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0275269"}},"subtitle":[],"editor":[{"given":"L. Michel","family":"Espinoza-Fonseca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":67,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0275269","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]}}}