{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:41:10Z","timestamp":1789713670332,"version":"4.0.1"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T00:00:00Z","timestamp":1525305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0196791","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T18:19:24Z","timestamp":1525371564000},"page":"e0196791","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["Pharmacological characterization of potent and selective NaV1.7 inhibitors engineered from Chilobrachys jingzhao tarantula venom peptide JzTx-V"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-3148","authenticated-orcid":true,"given":"Bryan D.","family":"Moyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin K.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ligutti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Favreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie H.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin","family":"Sham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licheng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"St\u00f6cklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyuan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anruo","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaustav","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Les P.","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,5,3]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jmb.2014.07.027","article-title":"From foe to friend: using animal toxins to investigate ion channel function","volume":"427","author":"J Kalia","year":"2015","journal-title":"Journal of molecular biology"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.neuropharm.2017.04.014","article-title":"The pharmacology of voltage-gated sodium channel activators","volume":"127","author":"JR Deuis","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref3","article-title":"Sodium channels and pain: from toxins to therapies","author":"FC Cardoso","year":"2017","journal-title":"British journal of pharmacology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/978-3-642-41588-3_10","article-title":"Animal toxins influence voltage-gated sodium channel function","volume":"221","author":"J Gilchrist","year":"2014","journal-title":"Handbook of experimental pharmacology"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1021\/acschemneuro.7b00406","article-title":"Selective Voltage-Gated Sodium Channel Peptide Toxins from Animal Venom: Pharmacological Probes and Analgesic Drug Development","volume":"9","author":"Y Wu","year":"2017","journal-title":"ACS chemical neuroscience"},{"issue":"4","key":"ref6","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.toxicon.2012.04.337","article-title":"Spider-venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutic leads","volume":"60","author":"JK Klint","year":"2012","journal-title":"Toxicon: official journal of the International Society on Toxinology"},{"issue":"6","key":"ref7","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.toxicon.2006.01.018","article-title":"Venom landscapes: mining the complexity of spider venoms via a combined cDNA and mass spectrometric approach","volume":"47","author":"P Escoubas","year":"2006","journal-title":"Toxicon: official journal of the International Society on Toxinology"},{"issue":"12","key":"ref8","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.3390\/toxins2122851","article-title":"Spider-venom peptides as therapeutics","volume":"2","author":"NJ Saez","year":"2010","journal-title":"Toxins"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrn3404","article-title":"The Na(V)1.7 sodium channel: from molecule to man","volume":"14","author":"SD Dib-Hajj","year":"2013","journal-title":"Nature reviews Neuroscience"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.pharmthera.2016.11.015","article-title":"NaV1.7 as a pain target\u2014From gene to pharmacology","volume":"172","author":"I Vetter","year":"2017","journal-title":"Pharmacology & therapeutics"},{"issue":"8","key":"ref11","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1517\/14728222.2016.1162295","article-title":"Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief","volume":"20","author":"EC Emery","year":"2016","journal-title":"Expert opinion on therapeutic targets"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1399-0004.2007.00790.x","article-title":"Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations","volume":"71","author":"YP Goldberg","year":"2007","journal-title":"Clinical genetics"},{"issue":"7121","key":"ref13","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/nature05413","article-title":"An SCN9A channelopathy causes congenital inability to experience pain","volume":"444","author":"JJ Cox","year":"2006","journal-title":"Nature"},{"issue":"3","key":"ref14","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1136\/jmg.2003.012153","article-title":"Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia","volume":"41","author":"Y Yang","year":"2004","journal-title":"Journal of medical genetics"},{"issue":"5","key":"ref15","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.neuron.2006.10.006","article-title":"SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes","volume":"52","author":"CR Fertleman","year":"2006","journal-title":"Neuron"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/ana.22485","article-title":"Gain of function Nanu1.7 mutations in idiopathic small fiber neuropathy","volume":"71","author":"CG Faber","year":"2012","journal-title":"Annals of neurology"},{"issue":"34","key":"ref17","doi-asserted-by":"crossref","first-page":"12706","DOI":"10.1073\/pnas.0404915101","article-title":"Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain","volume":"101","author":"MA Nassar","year":"2004","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/ncomms1795","article-title":"Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons","volume":"3","author":"MS Minett","year":"2012","journal-title":"Nature communications"},{"issue":"9","key":"ref19","doi-asserted-by":"crossref","first-page":"e105895","DOI":"10.1371\/journal.pone.0105895","article-title":"Global Nav1.7 knockout mice recapitulate the phenotype of human congenital indifference to pain","volume":"9","author":"J Gingras","year":"2014","journal-title":"PloS one"},{"issue":"18","key":"ref20","doi-asserted-by":"crossref","first-page":"7093","DOI":"10.1021\/jm501981g","article-title":"Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications","volume":"58","author":"M de Lera Ruiz","year":"2015","journal-title":"Journal of medicinal chemistry"},{"issue":"9","key":"ref21","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1021\/acschembio.7b00542","article-title":"Engineering Antibody Reactivity for Efficient Derivatization to Generate NaV1.7 Inhibitory GpTx-1","volume":"12","author":"K Biswas","year":"2017","journal-title":"Peptide-Antibody Conjugates. ACS chemical biology"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1021\/acs.jmedchem.5b01947","article-title":"Single Residue Substitutions That Confer Voltage-Gated Sodium Ion Channel Subtype Selectivity in the NaV1.7 Inhibitory Peptide GpTx-1","volume":"59","author":"JK Murray","year":"2016","journal-title":"Journal of medicinal chemistry"},{"issue":"21","key":"ref23","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1016\/j.bmcl.2015.06.033","article-title":"Sustained inhibition of the NaV1.7 sodium channel by engineered dimers of the domain II binding peptide GpTx-1","volume":"25","author":"JK Murray","year":"2015","journal-title":"Bioorganic & medicinal chemistry letters"},{"issue":"5","key":"ref24","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1021\/jm501765v","article-title":"Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel","volume":"58","author":"JK Murray","year":"2015","journal-title":"Journal of medicinal chemistry"},{"issue":"3","key":"ref25","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.toxicon.2006.10.012","article-title":"Isolation and characterization of Jingzhaotoxin-V, a novel neurotoxin from the venom of the spider Chilobrachys jingzhao","volume":"49","author":"X Zeng","year":"2007","journal-title":"Toxicon: official journal of the International Society on Toxinology"},{"issue":"7","key":"ref26","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.3390\/toxins6072177","article-title":"Molecular surface of JZTX-V (beta-Theraphotoxin-Cj2a) interacting with voltage-gated sodium channel subtype NaV1.4","volume":"6","author":"J Luo","year":"2014","journal-title":"Toxins"},{"issue":"17","key":"ref27","doi-asserted-by":"crossref","first-page":"6784","DOI":"10.1021\/acs.jmedchem.5b00495","article-title":"Pharmaceutical Optimization of Peptide Toxins for Ion Channel Targets: Potent, Selective, and Long-Lived Antagonists of Kv1.3","volume":"58","author":"JK Murray","year":"2015","journal-title":"Journal of medicinal chemistry"},{"issue":"36","key":"ref28","doi-asserted-by":"crossref","first-page":"24155","DOI":"10.1074\/jbc.M109.017764","article-title":"Hepcidin revisited, disulfide connectivity, dynamics, and structure","volume":"284","author":"JB Jordan","year":"2009","journal-title":"The Journal of biological chemistry"},{"issue":"43","key":"ref29","doi-asserted-by":"crossref","first-page":"10457","DOI":"10.1021\/bi00107a014","article-title":"Assignment of the natural abundance 13C spectrum of proteins using 13C 1H-detected heteronuclear multiple-bond correlation NMR spectroscopy: structural information and stereospecific assignments from two- and three-bond carbon-hydrogen coupling constants","volume":"30","author":"PE Hansen","year":"1991","journal-title":"Biochemistry"},{"issue":"4","key":"ref30","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10858-015-9924-9","article-title":"Combined automated NOE assignment and structure calculation with CYANA","volume":"62","author":"P Guntert","year":"2015","journal-title":"Journal of biomolecular NMR"},{"issue":"1","key":"ref31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1063\/1.1729860","article-title":"Contact Electron-Spin Coupling of Nuclear Magnetic Moments","volume":"30","author":"MJ Karplus","year":"1959","journal-title":"The Journal of chemical physics"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1124\/jpet.116.239590","article-title":"Pharmacologic Characterization of AMG8379, a Potent and Selective Small Molecule Sulfonamide Antagonist of the Voltage-Gated Sodium Channel NaV1.7","volume":"362","author":"TJ Kornecook","year":"2017","journal-title":"The Journal of pharmacology and experimental therapeutics"},{"issue":"4","key":"ref33","doi-asserted-by":"crossref","first-page":"e0152405","DOI":"10.1371\/journal.pone.0152405","article-title":"Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release","volume":"11","author":"AJ Alexandrou","year":"2016","journal-title":"PloS one"},{"issue":"3","key":"ref34","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.bbrc.2006.11.086","article-title":"Effects and mechanism of Chinese tarantula toxins on the Kv2.1 potassium channels","volume":"352","author":"C Yuan","year":"2007","journal-title":"Biochemical and biophysical research communications"},{"issue":"1","key":"ref35","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41598-017-01129-0","article-title":"The tarantula toxin beta\/delta-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity","volume":"7","author":"JS Wingerd","year":"2017","journal-title":"Scientific reports"},{"issue":"15","key":"ref36","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1111\/bph.13865","article-title":"Modulatory features of the novel spider toxin mu-TRTX-Df1a isolated from the venom of the spider Davus fasciatus","volume":"174","author":"FC Cardoso","year":"2017","journal-title":"British journal of pharmacology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"40883","DOI":"10.1038\/srep40883","article-title":"Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a","volume":"7","author":"JR Deuis","year":"2017","journal-title":"Scientific reports"},{"issue":"27","key":"ref38","doi-asserted-by":"crossref","first-page":"13974","DOI":"10.1074\/jbc.M116.725978","article-title":"Engineering Highly Potent and Selective Microproteins against Nav1.7 Sodium Channel for Treatment of Pain","volume":"291","author":"A Shcherbatko","year":"2016","journal-title":"The Journal of biological chemistry"},{"issue":"28","key":"ref39","doi-asserted-by":"crossref","first-page":"20392","DOI":"10.1074\/jbc.M112.426627","article-title":"Structure and function of hainantoxin-III, a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels isolated from the Chinese bird spider Ornithoctonus hainana","volume":"288","author":"Z Liu","year":"2013","journal-title":"The Journal of biological chemistry"},{"issue":"40","key":"ref40","doi-asserted-by":"crossref","first-page":"27300","DOI":"10.1074\/jbc.M708447200","article-title":"Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration","volume":"283","author":"Y Xiao","year":"2008","journal-title":"The Journal of biological chemistry"},{"issue":"31","key":"ref41","doi-asserted-by":"crossref","first-page":"22707","DOI":"10.1074\/jbc.M113.461392","article-title":"Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin huwentoxin-IV (mu-TRTX-Hh2a)","volume":"288","author":"NA Minassian","year":"2013","journal-title":"The Journal of biological chemistry"},{"issue":"10","key":"ref42","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1111\/bph.13081","article-title":"Seven novel modulators of the analgesic target NaV 1.7 uncovered using a high-throughput venom-based discovery approach","volume":"172","author":"JK Klint","year":"2015","journal-title":"British journal of pharmacology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"39662","DOI":"10.1038\/srep39662","article-title":"Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor","volume":"7","author":"M Flinspach","year":"2017","journal-title":"Scientific reports"},{"issue":"6","key":"ref44","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1124\/mol.110.066332","article-title":"The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation","volume":"78","author":"Y Xiao","year":"2010","journal-title":"Molecular pharmacology"},{"issue":"3","key":"ref45","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1124\/mol.107.041046","article-title":"Inhibition of sodium channel gating by trapping the domain II voltage sensor with protoxin II","volume":"73","author":"S Sokolov","year":"2008","journal-title":"Molecular pharmacology"},{"issue":"2","key":"ref46","doi-asserted-by":"crossref","DOI":"10.3390\/toxins10020064","article-title":"Selective Closed-State Nav1.7 Blocker JZTX-34 Exhibits Analgesic Effects against Pain","volume":"10","author":"X Zeng","year":"2018","journal-title":"Toxins"},{"issue":"2","key":"ref47","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1152\/jn.00944.2007","article-title":"Role of TTX-sensitive and TTX-resistant sodium channels in Adelta- and C-fiber conduction and synaptic transmission","volume":"99","author":"V Pinto","year":"2008","journal-title":"Journal of neurophysiology"},{"issue":"5","key":"ref48","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1124\/mol.108.047670","article-title":"ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors","volume":"74","author":"WA Schmalhofer","year":"2008","journal-title":"Molecular pharmacology"},{"issue":"2","key":"ref49","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/cne.21786","article-title":"Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons","volume":"510","author":"T Fukuoka","year":"2008","journal-title":"The Journal of comparative neurology"},{"issue":"2","key":"ref50","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.neures.2011.01.020","article-title":"Comparative study of voltage-gated sodium channel alpha-subunits in non-overlapping four neuronal populations in the rat dorsal root ganglion","volume":"70","author":"T Fukuoka","year":"2011","journal-title":"Neuroscience research"},{"issue":"1","key":"ref51","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.mcn.2010.08.017","article-title":"Single-cell analysis of sodium channel expression in dorsal root ganglion neurons","volume":"46","author":"C Ho","year":"2011","journal-title":"Molecular and cellular neurosciences"},{"key":"ref52","first-page":"285","article-title":"Correlation of the electrophysiological profiles and sodium channel transcripts of individual rat dorsal root ganglia neurons","volume":"8","author":"O Theriault","year":"2014","journal-title":"Frontiers in cellular neuroscience"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0196791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T13:15:34Z","timestamp":1589030134000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0196791"}},"subtitle":[],"editor":[{"given":"Zhe","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,5,3]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0196791","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,3]]}}}