{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:29:51Z","timestamp":1788532191385,"version":"build-2803163510"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"State Assignment","award":["124051400034-0"],"award-info":[{"award-number":["124051400034-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Snake venom variation has important clinical implications, yet individual-level venomics remains limited. We investigated inter- and intrapopulation variability in forest-steppe adder Vipera nikolskii and its recognition by commercial V. berus antivenom using proteomic and immunological approaches. Venoms from 12 individual V. nikolskii specimens representing two geographically distinct populations (BG and KM), together with three pooled V. nikolskii and one pooled V. berus samples were analyzed by LC\u2013MS\/MS, ELISA, Western blot, and pull-down assays. Multivariate analysis revealed relative homogeneity in BG and pronounced heterogeneity in KM venoms. Area-based proteomics revealed V. berus venom enrichment in PLA2 (34.6%), SVMP (14.6%), and CRiSP (15.6%), whereas V. nikolskii venoms were more variable. Pooled V. nikolskii venoms showed SVMP abundance (35.2\u201341.1%), contrasting with lower levels in individual samples. Antivenom binding was stronger for V. berus but weaker and more variable across individual and pooled V. nikolskii samples. Antivenom targeted PLA2\/VEGF, CRiSP (only in V. berus), and Kunitz-type proteins. In vivo neutralization assay demonstrated strong protection against V. berus but not V. nikolskii venom. These findings reveal substantial compositional and antigenic variability in V. nikolskii venoms, highlight discrepancies between pooled and individual ones, and underscore the need for region-specific and functionally validated antivenom evaluation.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00088","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T21:15:51Z","timestamp":1787519751000},"page":"4546-4562","source":"Crossref","is-referenced-by-count":0,"title":["Antivenomic\nand Proteomic Assessment of Inter- and\nIntrapopulation Venom Variations in Nikolsky\u2019s Adder\n                    <i>Vipera nikolskii<\/i>\n                    : Comparison to Common Adder\n                    <i>Vipera berus<\/i>"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5148-1182","authenticated-orcid":true,"given":"Elena","family":"Gondarenko","sequence":"first","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Arkhangelskaya","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Timakina","sequence":"additional","affiliation":[{"name":"Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , ,","place":["Pushchino, Russia, 142290"]},{"name":"Pushchino Branch of the Federal State Budgetary Educational Institution of Higher Education \u201cRussian Biotechnological University (BIOTECH University)\u201d , ,","place":["Pushchino, Russia, 142290"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8949-5600","authenticated-orcid":true,"given":"Vladimir","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , ,","place":["Pushchino, Russia, 142290"]},{"name":"Pushchino Branch of the Federal State Budgetary Educational Institution of Higher Education \u201cRussian Biotechnological University (BIOTECH University)\u201d , ,","place":["Pushchino, Russia, 142290"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Dyachenko","sequence":"additional","affiliation":[{"name":"Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , ,","place":["Pushchino, Russia, 142290"]},{"name":"Pushchino Branch of the Federal State Budgetary Educational Institution of Higher Education \u201cRussian Biotechnological University (BIOTECH University)\u201d , ,","place":["Pushchino, Russia, 142290"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Starkov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Kasheverov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Utkin","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Tsetlin","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-9193","authenticated-orcid":true,"given":"Denis","family":"Kudryavtsev","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , , ,","place":["Moscow, Russia, 117997"]},{"name":"Sechenov university , , ,","place":["Moscow, Russia, 105043"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"2026090409132428900_cit1","first-page":"293","article-title":"Vipera (Pelias) [berus] nikolskii\nVedmederja, Grubant & Rudaeva, 1986\u2013Waldsteppenotter","volume":"3\/IIB","author":"Bakiev","year":"2005","journal-title":"Handb. Rept. Amphib. Eur."},{"key":"2026090409132428900_cit2","first-page":"359","volume-title":"True Vipers: Natural\nHistory and Toxinology of Old World Vipers","author":"Mallow","year":"2003"},{"key":"2026090409132428900_cit3","doi-asserted-by":"publisher","DOI":"10.1111\/mec.70019","article-title":"Unveiling the Evolutionary History\nof European Vipers and Their Venoms From a Multi-Omic Approach","volume":"34","author":"Talavera","year":"2025","journal-title":"Mol. Ecol."},{"key":"2026090409132428900_cit4","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1006\/mpev.2001.0912","article-title":"Evolutionary Relationships\namong the True Vipers (Reptilia: Viperidae) inferred from mitochondrial\nDNA sequences","volume":"19","author":"Lenk","year":"2001","journal-title":"Mol. Phylogenet. Evol."},{"key":"2026090409132428900_cit5","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11020090","article-title":"Vipera berus\n            berus Venom from Russia:\nVenomics, Bioactivities\nand Preclinical Assessment of Microgen Antivenom","volume":"11","author":"Al-Shekhadat","year":"2019","journal-title":"Toxins"},{"key":"2026090409132428900_cit6","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13060427","article-title":"Old World Vipers\u2013A Review\nabout Snake Venom Proteomics of Viperinae and Their Variations","volume":"13","author":"Damm","year":"2021","journal-title":"Toxins"},{"key":"2026090409132428900_cit7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.152724","article-title":"Vipers of Major Clinical Relevance in Europe: Taxonomy,\nvenom composition, toxicology and clinical management of human bites","volume":"453","author":"Di Nicola","year":"2021","journal-title":"Toxicology"},{"key":"2026090409132428900_cit8","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8040105","article-title":"Quantitative\nProteomic Analysis of Venoms from Russian Vipers of Pelias Group:\nPhospholipases A2 are the Main Venom Components","volume":"8","author":"Kovalchuk","year":"2016","journal-title":"Toxins"},{"key":"2026090409132428900_cit9","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1021\/acs.jproteome.9b00120","article-title":"Comprehensive\nStudy of the Proteome and Transcriptome of the Venom of the Most Venomous\nEuropean Viper: Discovery of a New Subclass of Ancestral Snake Venom\nMetalloproteinase Precursor-Derived Proteins","volume":"18","author":"Leonardi","year":"2019","journal-title":"J. Proteome Res."},{"key":"2026090409132428900_cit10","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.toxicon.2017.06.004","article-title":"Individual Variability of Venom from\nthe European Adder (Vipera berus berus)\nfrom one locality in Eastern Hungary","volume":"135","author":"Malina","year":"2017","journal-title":"Toxicon"},{"key":"2026090409132428900_cit11","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.biochi.2026.01.018","article-title":"Comparison\nof proteomes and biofunctional properties\nof male and female common adder (Vipera berus) venoms","volume":"244","author":"Schulte","year":"2026","journal-title":"Biochimie."},{"key":"2026090409132428900_cit12","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.toxicon.2007.11.001","article-title":"Heterodimeric neurotoxic\nphospholipases\nA2 \u2013 the first proteins from venom of recently established\nspecies Vipera nikolskii: implication\nof venom composition in viper systematics","volume":"51","author":"Ramazanova","year":"2008","journal-title":"Toxicon"},{"key":"2026090409132428900_cit13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001194","article-title":"Reappraisal of Vipera aspis Venom Neurotoxicity","volume":"2","author":"Ferquel","year":"2007","journal-title":"PLoS\nOne"},{"key":"2026090409132428900_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2022.104613","article-title":"Interpopulational\nVariation and Ontogenetic\nShift in the Venom Composition of Lataste\u2019s Viper (Vipera latastei, Bosca\u0301 1878) from northern Portugal","volume":"263","author":"Avella","year":"2022","journal-title":"J. Proteomics"},{"key":"2026090409132428900_cit15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jprot.2019.02.004","article-title":"Intact\nProtein Mass Spectrometry\nReveals Intraspecies Variations in Venom Composition of a Local Population\nof Vipera kaznakovi in Northeastern Turkey","volume":"199","author":"Petras","year":"2019","journal-title":"J. Proteomics"},{"key":"2026090409132428900_cit16","unstructured":"World Health Organization.\n          . Guidelines for\nthe production, control and regulation of snake antivenom immunoglobulinsWHO Tech Rep. Ser.2017; Vol. 1004 Annex 5."},{"issue":"3","key":"2026090409132428900_cit17","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3109\/15563650.2012.660695","article-title":"European Viper Envenomings:\nAssessment of Viperfav and Other Symptomatic Treatments","volume":"50","author":"Boels","year":"2012","journal-title":"Clin. Toxicol."},{"key":"2026090409132428900_cit18","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.3390\/toxins6082471","article-title":"Immunological\nCross-Reactivity and Neutralisation of European Viper Venoms with\nthe Monospecific Vipera berus Antivenom\nViperaTAb","volume":"6","author":"Casewell","year":"2014","journal-title":"Toxins"},{"key":"2026090409132428900_cit19","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1042\/BCJ20160577","article-title":"Venomics:\nIntegrative Venom Proteomics and Beyond","volume":"474","author":"Calvete","year":"2017","journal-title":"Biochem.\nJ."},{"key":"2026090409132428900_cit20","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci11120605","article-title":"The Venom of Vipera ammodytes ammodytes: Proteomics, Neurotoxic Effect\nand Neutralization by Antivenom","volume":"11","author":"Ivanovic\u0301","year":"2024","journal-title":"Vet. Sci."},{"key":"2026090409132428900_cit21","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14110723","article-title":"A Review\nof the Proteomic Profiling\nof African Viperidae and Elapidae Snake Venoms and Their Antivenom\nNeutralisation","volume":"14","author":"Offor","year":"2022","journal-title":"Toxins"},{"issue":"2","key":"2026090409132428900_cit22","doi-asserted-by":"publisher","first-page":"150","DOI":"10.15393\/j1.art.2018.7542","article-title":"\u201cDose-response\u201d\nmodels with mixed parameters by the example of venom toxicity estimation\nof the common European adder Vipera berus","volume":"7","author":"Shitikov","year":"2018","journal-title":"Principy e\u0300kologii."},{"key":"2026090409132428900_cit23","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11030149","article-title":"Preclinical Assessment\nof a New Polyvalent Antivenom (Inoserp Europe)\nagainst Several Species of the Subfamily Viperinae","volume":"11","author":"Garci\u0301a-Arredondo","year":"2019","journal-title":"Toxins"},{"issue":"1","key":"2026090409132428900_cit24","doi-asserted-by":"publisher","DOI":"10.1002\/cpph.43","article-title":"The Irwin Test and Functional Observational Battery\n(FOB) for Assessing the Effects of Compounds on Behavior, Physiology,\nand Safety Pharmacology in Rodents","volume":"83","author":"Mathiasen","year":"2018","journal-title":"Curr. Protoc.\nPharmacol."},{"key":"2026090409132428900_cit25","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1134\/S1607672925600137","article-title":"Intravenous\nAdministration of Heterodimeric Phospholipase A2 HDP-1 Disturbs Cardiovascular\nSystem Functions and Biochemical Composition of Blood in Anesthetized\nRats","volume":"522","author":"Ismailova","year":"2025","journal-title":"Dokl. Biochem. Biophys."},{"issue":"2","key":"2026090409132428900_cit26","doi-asserted-by":"publisher","DOI":"10.3390\/toxins16020100","article-title":"Effects of the Heterodimeric\nNeurotoxic Phospholipase A2 from the Venom of Vipera nikolskii on the Contractility of Rat Papillary Muscles\nand Thoracic Aortas","volume":"16","author":"Averin","year":"2024","journal-title":"Toxins (Basel)."},{"key":"2026090409132428900_cit27","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9010015","article-title":"Snake Venom\nMetalloproteinases and Their Peptide Inhibitors\nfrom Myanmar Russell\u2019s Viper Venom","volume":"9","author":"Yee","year":"2017","journal-title":"Toxins"},{"key":"2026090409132428900_cit28","doi-asserted-by":"publisher","DOI":"10.1186\/1678-9199-20-23","article-title":"Snake Venom L-Amino Acid Oxidases:\nAn Overview on Their\nAntitumor Effects","volume":"20","author":"Costa","year":"2014","journal-title":"J. Venom. Anim. Toxins Incl.\nTrop. Dis."},{"key":"2026090409132428900_cit29","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10100393","article-title":"Antibody\nCross-Reactivity in Antivenom Research","volume":"10","author":"Ledsgaard","year":"2018","journal-title":"Toxins"},{"key":"2026090409132428900_cit30","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jprot.2018.07.007","article-title":"Compositional and Functional Investigation\nof Individual\nand Pooled Venoms from long-term captive and recently wild-caught\nBothrops jararaca snakes","volume":"186","author":"Galizio","year":"2018","journal-title":"J. Proteomics"},{"key":"2026090409132428900_cit31","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14040235","article-title":"Immunorecognition\nand Neutralization of Crotalus durissus cumanensis Venom by a Commercial Antivenom Produced in Colombia","volume":"14","author":"Acosta-Pen\u0303a","year":"2022","journal-title":"Toxins"},{"key":"2026090409132428900_cit32","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1590\/S1678-91992009000300008","article-title":"IgG Antibodies against Phospholipase\nA2 from Crotalus durissus terrificus neutralize the\nlethal activity of the venom","volume":"15","author":"Rodri\u0301guez","year":"2009","journal-title":"J. Venom. Anim.\nToxins Incl. Trop. Dis."},{"issue":"1","key":"2026090409132428900_cit33","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00353-21","article-title":"A Practical Guide\nto Small Protein Discovery and Characterization Using Mass Spectrometry","volume":"204","author":"Ahrens","year":"2022","journal-title":"J. Bacteriol."},{"issue":"23\u201324","key":"2026090409132428900_cit34","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202100008","article-title":"Bottom-Up and Top-Down Proteomic Approaches for the\nIdentification, Characterization, and Quantification of the Low Molecular\nWeight Proteome with Focus on Short Open Reading Frame-Encoded Peptides","volume":"21","author":"Cassidy","year":"2021","journal-title":"Proteomics"},{"key":"2026090409132428900_cit35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005768","article-title":"Cross-Recognition\nof a Pit Viper\nPolyspecific Antivenom Explored through High-Density Peptide Microarray\nEpitope Mapping","volume":"11","author":"Engmark","year":"2017","journal-title":"PLoS Negl. Trop. Dis."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.6c00088","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/9\/4546\/67066135\/acs.jproteome.6c00088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/9\/4546\/67066135\/acs.jproteome.6c00088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:11:25Z","timestamp":1788531085000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/25\/9\/4546\/5293759\/Antivenomic-and-Proteomic-Assessment-of-Inter-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,8,22]]},"published-print":{"date-parts":[[2026,9,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.6c00088","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]}}}