{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:01:35Z","timestamp":1789405295566,"version":"build-2803163510"},"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00c3fico e Tecnol\u00c3\u00b3gico","doi-asserted-by":"publisher","award":["309940\/2019-2"],"award-info":[{"award-number":["309940\/2019-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00c3fico e Tecnol\u00c3\u00b3gico","doi-asserted-by":"publisher","award":["403193\/2022-2"],"award-info":[{"award-number":["403193\/2022-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00c3\u00a7\u00c3\u00a3o de Amparo \u00c3\u00a0 Pesquisa do Estado de S\u00c3\u00a3o Paulo","doi-asserted-by":"publisher","award":["2024\/13327-2"],"award-info":[{"award-number":["2024\/13327-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00c3\u00a7\u00c3\u00a3o de Amparo \u00c3\u00a0 Pesquisa do Estado de S\u00c3\u00a3o Paulo","doi-asserted-by":"publisher","award":["2020\/08615-8"],"award-info":[{"award-number":["2020\/08615-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00c3\u00a7\u00c3\u00a3o de Amparo \u00c3\u00a0 Pesquisa do Estado de S\u00c3\u00a3o Paulo","doi-asserted-by":"publisher","award":["2024\/01956-5"],"award-info":[{"award-number":["2024\/01956-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Climate change has facilitated the spread of arboviruses like the Chikungunya virus (CHIKV). CHIKV, a re-emerging virus from the\n                    <jats:italic>Togaviridae<\/jats:italic>\n                    family, has caused numerous global outbreaks. The absence of antiviral therapy against CHIKV poses a significant threat to public health. The cleavage of the viral polyprotein relies on the catalytic activity of nsP2, crucial for viral replication. Therefore the nsP2 protease presents a promising target for antiviral drug development. Animal venom-derived peptides demonstrated potential in combating various diseases including infections, cancer, and neurodegenerative disorders. In this study, we assessed the inhibitory effects of pantinin-1, a peptide derived from the scorpion\n                    <jats:italic>Pandinus imperator<\/jats:italic>\n                    with broad antimicrobial activity, against CHIKV nsP2 protease. Pantinin-1 effectively inhibited CHIKV nsP2 protease, with a half-maximal inhibitory concentration (IC\u2085\u2080) of 6.4\u2009\u00b1\u20092.04 \u00b5M and complete inhibition at 175 \u00b5M. Further examination revealed that pantinin-1 functions as a competitive inhibitor with low micromolar affinity and exhibited no toxicity up to 20 \u00b5M in cell culture. Using docking and molecular dynamics simulations, the protein-peptide interaction was analyzed, and the key residues involved in the protease binding were predicted. These findings underscore the potential of pantinin-1 as a lead candidate targeting nsP2 protease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0346930","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T17:29:17Z","timestamp":1775755757000},"page":"e0346930","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of Chikungunya virus nsP2 protease in vitro by scorpion venom peptide pantinin-1"],"prefix":"10.1371","volume":"21","author":[{"given":"Mohammadamin","family":"Mastalipour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nika Aparecida","family":"Coronado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-8677","authenticated-orcid":true,"given":"Jorge Enrique","family":"Hern\u00e1ndez Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Willbold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-3884","authenticated-orcid":true,"given":"Raphael Josef","family":"Eberle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"issue":"4","key":"pone.0346930.ref001","doi-asserted-by":"crossref","DOI":"10.1136\/bmjgh-2021-007735","article-title":"Socioeconomic risk markers of arthropod-borne virus (arbovirus) infections: a systematic literature review and meta-analysis","volume":"7","author":"GM Power","year":"2022","journal-title":"BMJ Glob Health"},{"key":"pone.0346930.ref002","doi-asserted-by":"crossref","first-page":"100139","DOI":"10.1016\/j.crpvbd.2023.100139","article-title":"Temperature and transmission of chikungunya, dengue, and Zika viruses: a systematic review of experimental studies on Aedes aegypti and Aedes albopictus","volume":"4","author":"M Delrieu","year":"2023","journal-title":"Curr Res Parasitol Vector Borne Dis"},{"issue":"4","key":"pone.0346930.ref003","article-title":"The worldwide seroprevalence of DENV, CHIKV and ZIKV infection: A systematic review and meta-analysis","volume":"15","author":"Z Li","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"pone.0346930.ref004","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.idc.2019.08.006","article-title":"Chikungunya: epidemiology, pathogenesis, clinical features, management, and prevention","volume":"33","author":"F Vairo","year":"2019","journal-title":"Infect Dis Clin North Am"},{"issue":"2","key":"pone.0346930.ref005","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.azn.2025.01.003","article-title":"Progress in the molecular epidemiology of chikungunya virus","volume":"1","author":"D Zhang","year":"2025","journal-title":"Anim Zoonoses"},{"issue":"2","key":"pone.0346930.ref006","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0012810","article-title":"Clinical manifestations associated with the chronic phase of Chikungunya fever: a systematic review of prevalence","volume":"19","author":"RA Santiago","year":"2025","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"pone.0346930.ref007","doi-asserted-by":"crossref","first-page":"946","DOI":"10.4269\/ajtmh.21-0189","article-title":"Clinical features of acute Chikungunya virus infection in children and adults during an outbreak in the Maldives","volume":"105","author":"HA Imad","year":"2021","journal-title":"Am J Trop Med Hyg"},{"issue":"7","key":"pone.0346930.ref008","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/trstmh\/try063","article-title":"Chikungunya chronic disease: a systematic review and meta-analysis","volume":"112","author":"ES Paix\u00e3o","year":"2018","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"2","key":"pone.0346930.ref009","first-page":"89985","article-title":"Long chikungunya? An overview to immunopathology of persistent arthralgia","volume":"13","author":"JEP Silveira-Freitas","year":"2024","journal-title":"World J Virol"},{"issue":"2","key":"pone.0346930.ref010","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.pneurobio.2009.12.006","article-title":"Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus","volume":"91","author":"T Das","year":"2010","journal-title":"Prog Neurobiol"},{"key":"pone.0346930.ref011","doi-asserted-by":"crossref","first-page":"129949","DOI":"10.1016\/j.ijbiomac.2024.129949","article-title":"Drugs targeting structural and nonstructural proteins of the chikungunya virus: a review","volume":"262","author":"M Wang","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"pone.0346930.ref012","first-page":"75","article-title":"Functions of Chikungunya Virus Nonstructural Proteins.","author":"T Ahola","year":"2016","journal-title":"Chikungunya Virus: Advances in Biology, Pathogenesis, and Treatment. Cham, Switzerland: Springer Internat. Publ"},{"key":"pone.0346930.ref013","first-page":"63","article-title":"Function of Chikungunya virus structural proteins.","author":"SW Metz","year":"2016","journal-title":"Chikungunya Virus: Advances in Biology, Pathogenesis, and Treatment. Cham, Switzerland: Springer Internat. Publ."},{"issue":"9","key":"pone.0346930.ref014","doi-asserted-by":"crossref","first-page":"5635","DOI":"10.1074\/jbc.M113.503433","article-title":"Functional cross-talk between distant domains of chikungunya virus non-structural protein 2 is decisive for its RNA-modulating activity","volume":"289","author":"PK Das","year":"2014","journal-title":"J Biol Chem"},{"issue":"18","key":"pone.0346930.ref015","doi-asserted-by":"crossref","first-page":"16505","DOI":"10.1021\/acs.jmedchem.4c01346","article-title":"Structure activity of \u03b2-amidomethyl vinyl sulfones as covalent inhibitors of Chikungunya nsP2 cysteine protease with antialphavirus activity","volume":"67","author":"A Ghoshal","year":"2024","journal-title":"J Med Chem"},{"key":"pone.0346930.ref016","doi-asserted-by":"crossref","first-page":"37124","DOI":"10.1038\/srep37124","article-title":"Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease\u2019s active site cysteine residue","volume":"6","author":"K Rausalu","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0346930.ref017","first-page":"100376","article-title":"Novel peptide inhibitor for the Chikungunya virus nsP2 protease: identification and characterization","volume":"8","author":"M Mastalipour","year":"2025","journal-title":"Curr Res Microb Sci"},{"issue":"3","key":"pone.0346930.ref018","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0246319","article-title":"In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases","volume":"16","author":"RJ Eberle","year":"2021","journal-title":"PLoS One"},{"issue":"10394","key":"pone.0346930.ref019","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1016\/S0140-6736(23)00641-4","article-title":"Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial","volume":"401","author":"M Schneider","year":"2023","journal-title":"Lancet"},{"issue":"10487","key":"pone.0346930.ref020","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/S0140-6736(25)00345-9","article-title":"Chikungunya virus virus-like particle vaccine safety and immunogenicity in adolescents and adults in the USA: a phase 3, randomised, double-blind, placebo-controlled trial","volume":"405","author":"JS Richardson","year":"2025","journal-title":"Lancet"},{"issue":"12","key":"pone.0346930.ref021","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3390\/toxins16120512","article-title":"Toxins from animal Venom-A rich source of active compounds with high pharmacological potential","volume":"16","author":"EN Lyukmanova","year":"2024","journal-title":"Toxins (Basel)"},{"issue":"4","key":"pone.0346930.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0061700","article-title":"Bee venom and its component apamin as neuroprotective agents in a Parkinson disease mouse model","volume":"8","author":"D Alvarez-Fischer","year":"2013","journal-title":"PLoS One"},{"key":"pone.0346930.ref023","doi-asserted-by":"crossref","first-page":"586705","DOI":"10.3389\/fphar.2020.586705","article-title":"Patagonin-CRISP: Antimicrobial Activity and Source of Antimicrobial Molecules in Duvernoy\u2019s Gland Secretion (Philodryas patagoniensis Snake)","volume":"11","author":"JC Badari","year":"2021","journal-title":"Front Pharmacol"},{"key":"pone.0346930.ref024","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1021\/acschemneuro.4c00089","article-title":"A snake venom peptide and its derivatives prevent A\u03b242 aggregation and eliminate toxic A\u03b242 aggregates in vitro","volume":"15","author":"LC Camargo","year":"2024","journal-title":"ACS Chem Neurosci"},{"issue":"3","key":"pone.0346930.ref025","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3390\/toxins17030136","article-title":"Innovations in Snake venom-derived therapeutics: a systematic review of global patents and their pharmacological applications","volume":"17","author":"DC Zona Rubio","year":"2025","journal-title":"Toxins (Basel)"},{"issue":"10","key":"pone.0346930.ref026","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd1197","article-title":"Therapeutic potential of venom peptides","volume":"2","author":"RJ Lewis","year":"2003","journal-title":"Nat Rev Drug Discov"},{"issue":"2","key":"pone.0346930.ref027","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3390\/toxins13020147","article-title":"Cell-penetrating peptides derived from animal venoms and toxins","volume":"13","author":"G R\u00e1dis-Baptista","year":"2021","journal-title":"Toxins (Basel)"},{"issue":"30","key":"pone.0346930.ref028","doi-asserted-by":"crossref","first-page":"20983","DOI":"10.1074\/jbc.M602168200","article-title":"Latarcins, antimicrobial and cytolytic peptides from the venom of the spider Lachesana tarabaevi (Zodariidae) that exemplify biomolecular diversity","volume":"281","author":"SA Kozlov","year":"2006","journal-title":"J Biol Chem"},{"key":"pone.0346930.ref029","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1471-2180-14-140","article-title":"Identification of natural antimicrobial agents to treat dengue infection: in vitro analysis of latarcin peptide activity against dengue virus","volume":"14","author":"HA Rothan","year":"2014","journal-title":"BMC Microbiol"},{"issue":"7","key":"pone.0346930.ref030","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/j.peptides.2011.05.015","article-title":"Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses","volume":"32","author":"Q Li","year":"2011","journal-title":"Peptides"},{"key":"pone.0346930.ref031","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.peptides.2013.03.026","article-title":"Three new antimicrobial peptides from the scorpion Pandinus imperator","volume":"45","author":"X-C Zeng","year":"2013","journal-title":"Peptides"},{"issue":"11","key":"pone.0346930.ref032","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1016\/j.bbamem.2018.08.012","article-title":"Biophysical characterization and antitumor activity of synthetic Pantinin peptides from scorpion\u2019s venom","volume":"1860","author":"E Jr Crusca","year":"2018","journal-title":"Biochim Biophys Acta Biomembr"},{"issue":"2863","key":"pone.0346930.ref033","first-page":"37","article-title":"Venomous drugs: ShK","volume":"214","author":"JM Crow","year":"2012","journal-title":"New Scientist"},{"issue":"10","key":"pone.0346930.ref034","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3390\/toxins11100564","article-title":"Snake venoms in drug discovery: valuable therapeutic tools for life saving","volume":"11","author":"T Mohamed Abd El-Aziz","year":"2019","journal-title":"Toxins (Basel)"},{"issue":"3","key":"pone.0346930.ref035","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1023\/A:1006457903545","article-title":"Contortrostatin, a dimeric disintegrin from contortrix contortrix, inhibits breast cancer progression","volume":"61","author":"Q Zhou","year":"2000","journal-title":"Breast Cancer Res Treat"},{"issue":"5","key":"pone.0346930.ref036","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3390\/ph15050540","article-title":"Design of D-amino acids SARS-CoV-2 main protease inhibitors using the cationic peptide from Rattlesnake venom as a scaffold","volume":"15","author":"RJ Eberle","year":"2022","journal-title":"Pharmaceuticals (Basel)"},{"issue":"11","key":"pone.0346930.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0112351","article-title":"Phospholipase A2 isolated from the venom of Crotalus durissus terrificus inactivates dengue virus and other enveloped viruses by disrupting the viral envelope","volume":"9","author":"VD Muller","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"pone.0346930.ref038","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0166-3542(94)90042-6","article-title":"Echinhibin-1--an inhibitor of Sendai virus isolated from the venom of the snake Echis coloratus","volume":"23","author":"G Borkow","year":"1994","journal-title":"Antiviral Res"},{"issue":"7","key":"pone.0346930.ref039","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1007\/s12098-010-0326-4","article-title":"Role of hemocoagulase in pulmonary hemorrhage in preterm infants: a systematic review","volume":"78","author":"A Lodha","year":"2011","journal-title":"Indian J Pediatr"},{"issue":"21","key":"pone.0346930.ref040","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1021\/acs.biochem.5b00992","article-title":"Kinetic, mutational, and structural studies of the venezuelan equine encephalitis virus nonstructural protein 2 cysteine protease","volume":"55","author":"X Hu","year":"2016","journal-title":"Biochemistry"},{"issue":"8","key":"pone.0346930.ref041","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.neuint.2008.02.009","article-title":"Physiological significance of high- and low-affinity agonist binding to neuronal and recombinant AMPA receptors","volume":"52","author":"M Kessler","year":"2008","journal-title":"Neurochem Int"},{"issue":"8016","key":"pone.0346930.ref042","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"J Abramson","year":"2024","journal-title":"Nature"},{"issue":"27","key":"pone.0346930.ref043","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1002\/jcc.25874","article-title":"GalaxyTongDock: symmetric and asymmetric ab initio protein-protein docking web server with improved energy parameters","volume":"40","author":"T Park","year":"2019","journal-title":"J Comput Chem"},{"issue":"2","key":"pone.0346930.ref044","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking","volume":"12","author":"D Kozakov","year":"2017","journal-title":"Nat Protoc"},{"key":"pone.0346930.ref045","article-title":"HDOCK: a web server for protein-protein and protein-DNA\/RNA docking based on a hybrid strategy","volume":"45","author":"Y Yan","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pone.0346930.ref046","volume-title":"Amber 2022","author":"DA Case","year":"2022"},{"issue":"1","key":"pone.0346930.ref047","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1021\/acs.jctc.9b00591","article-title":"ff19SB: amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution","volume":"16","author":"C Tian","year":"2020","journal-title":"J Chem Theory Comput"},{"key":"pone.0346930.ref048","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1021\/jz501780a","article-title":"Building water models: a different approach","volume":"5","author":"S Izadi","year":"2014","journal-title":"J Phys Chem Lett"},{"issue":"9","key":"pone.0346930.ref049","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py: an efficient program for end-state free energy calculations","volume":"8","author":"BR 3rd Miller","year":"2012","journal-title":"J Chem Theory Comput"},{"issue":"4","key":"pone.0346930.ref050","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1021\/ct3010485","article-title":"Improved generalized born solvent model parameters for protein simulations","volume":"9","author":"H Nguyen","year":"2013","journal-title":"J Chem Theory Comput"},{"key":"pone.0346930.ref051","article-title":"Dengue, Yellow Fever, Zika and Chikungunya epidemic arboviruses in Brazil: ultrastructural aspects","volume":"115","author":"DF Barreto-Vieira","year":"2021","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"4","key":"pone.0346930.ref052","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/pm\/pny132","article-title":"Intrathecal therapy for chronic pain: a review of Morphine and Ziconotide as Firstline Options","volume":"20","author":"TR Deer","year":"2019","journal-title":"Pain Med"},{"issue":"5","key":"pone.0346930.ref053","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1533-2500.2009.00303.x","article-title":"Intrathecal ziconotide for neuropathic pain: a review","volume":"9","author":"RL Rauck","year":"2009","journal-title":"Pain Pract"},{"issue":"6","key":"pone.0346930.ref054","doi-asserted-by":"crossref","first-page":"948","DOI":"10.3390\/v16060948","article-title":"Antiviral activities of mastoparan-L-derived peptides against human alphaherpesvirus 1","volume":"16","author":"LCP Vilas Boas","year":"2024","journal-title":"Viruses"},{"key":"pone.0346930.ref055","article-title":"Dermaseptins, multifunctional antimicrobial peptides: a review of their pharmacology, effectivity, mechanism of action, and possible future directions","volume":"10","author":"EJH Bartels","year":"2019","journal-title":"Front Pharmacol"},{"issue":"1","key":"pone.0346930.ref056","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3390\/microorganisms14010068","article-title":"Scorpion venom-derived peptides: a new weapon against carbapenem-resistant Acinetobacter baumannii","volume":"14","author":"C Capasso","year":"2026","journal-title":"Microorganisms"},{"key":"pone.0346930.ref057","doi-asserted-by":"crossref","first-page":"1569719","DOI":"10.3389\/fmicb.2025.1569719","article-title":"The inhibitory potential of three scorpion venom peptides against multidrug-resistant Klebsiella pnemoniae","volume":"16","author":"R Giugliano","year":"2025","journal-title":"Front Microbiol"},{"issue":"7","key":"pone.0346930.ref058","doi-asserted-by":"crossref","first-page":"713","DOI":"10.3390\/pathogens14070713","article-title":"Expanding the antiviral spectrum of scorpion-derived peptides against Toscana virus and Schmallenberg virus","volume":"14","author":"R Giugliano","year":"2025","journal-title":"Pathogens"},{"issue":"19","key":"pone.0346930.ref059","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202500333","article-title":"Pantinin-derived peptides against veterinary Herpesviruses: activity and structural characterization","volume":"20","author":"R Giugliano","year":"2025","journal-title":"ChemMedChem"},{"issue":"42","key":"pone.0346930.ref060","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2409166121","article-title":"Identification of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach","volume":"121","author":"EM Merten","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0346930.ref061","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/B978-0-12-803752-2.00006-5","article-title":"Enzymes as Drug Targets","author":"TP Kenakin","year":"2017","journal-title":"Pharmacology in Drug Discovery and Development"},{"issue":"3","key":"pone.0346930.ref062","first-page":"257","article-title":"Inhibition mechanism of lecithin-dependent hemolysin from Vibrio parahaemolyticus by flavonoids: an enzyme kinetic and structural approach","volume":"15","author":"FJ Vazquez-Armenta","year":"2025","journal-title":"Catal"},{"issue":"10","key":"pone.0346930.ref063","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.4049\/jimmunol.1501188","article-title":"A Brucella spp. protease inhibitor limits antigen lysosomal proteolysis, increases cross-presentation, and enhances CD8+ T Cell Responses","volume":"196","author":"LM Coria","year":"2016","journal-title":"J Immunol"},{"issue":"6","key":"pone.0346930.ref064","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1021\/cb400027q","article-title":"Structural basis for enzyme I inhibition by \u03b1-ketoglutarate","volume":"8","author":"V Venditti","year":"2013","journal-title":"ACS Chem Biol"},{"issue":"1","key":"pone.0346930.ref065","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00424-018-2241-x","article-title":"Substrates and inhibitors of phosphate transporters: from experimental tools to pathophysiological relevance","volume":"471","author":"V Sorribas","year":"2019","journal-title":"Pflugers Arch Eur J Physiol"},{"issue":"1","key":"pone.0346930.ref066","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3390\/biom14010099","article-title":"A Review of CYP-mediated drug interactions: mechanisms and in vitro drug-drug interaction assessment","volume":"14","author":"J Lee","year":"2024","journal-title":"Biomolecules"},{"issue":"12","key":"pone.0346930.ref067","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012816","article-title":"Withaferin A inhibits Chikungunya virus nsP2 protease and shows antiviral activity in the cell culture and mouse model of virus infection","volume":"20","author":"KB Sharma","year":"2024","journal-title":"PLoS Pathog"},{"key":"pone.0346930.ref068","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.biochi.2018.04.004","article-title":"Chikungunya virus inhibition by peptidomimetic inhibitors targeting virus-specific cysteine protease","volume":"149","author":"H Singh","year":"2018","journal-title":"Biochimie"},{"issue":"7","key":"pone.0346930.ref069","article-title":"MBZM-N-IBT, a novel small molecule, restricts Chikungunya virus infection by targeting nsP2 protease activity in vitro, in vivo, and ex vivo","volume":"66","author":"S De","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0346930.ref070","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ijbiomac.2018.05.007","article-title":"Crystal structure of chikungunya virus nsP2 cysteine protease reveals a putative flexible loop blocking its active site","volume":"116","author":"M Narwal","year":"2018","journal-title":"Int J Biol Macromol"},{"key":"pone.0346930.ref071","first-page":"62","article-title":"Current challenges in peptide-based drug discovery","volume":"2","author":"L Jr Otvos","year":"2014","journal-title":"Front Chem"},{"issue":"1","key":"pone.0346930.ref072","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: current status and future directions","volume":"20","author":"K Fosgerau","year":"2015","journal-title":"Drug Discov Today"},{"issue":"10","key":"pone.0346930.ref073","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1016\/j.bmc.2017.06.052","article-title":"Therapeutic peptides: historical perspectives, current development trends, and future directions","volume":"26","author":"JL Lau","year":"2018","journal-title":"Bioorg Med Chem"},{"issue":"3","key":"pone.0346930.ref074","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrmicro1098","article-title":"Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?","volume":"3","author":"KA Brogden","year":"2005","journal-title":"Nat Rev Microbiol"},{"key":"pone.0346930.ref075","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.toxicon.2014.06.006","article-title":"Antimicrobial peptides from scorpion venoms","volume":"88","author":"PL Harrison","year":"2014","journal-title":"Toxicon"},{"issue":"1","key":"pone.0346930.ref076","article-title":"Antimicrobial peptides","volume":"26","author":"L-J Zhang","year":"2016","journal-title":"Curr Biol"},{"issue":"12","key":"pone.0346930.ref077","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nbt1267","article-title":"Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies","volume":"24","author":"REW Hancock","year":"2006","journal-title":"Nat Biotechnol"},{"issue":"28","key":"pone.0346930.ref078","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.2174\/138161210793292555","article-title":"Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization","volume":"16","author":"L Gentilucci","year":"2010","journal-title":"Curr Pharm Des"},{"key":"pone.0346930.ref079","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fcimb.2016.00194","article-title":"Antimicrobial peptides: an emerging category of therapeutic agents","volume":"6","author":"M Mahlapuu","year":"2016","journal-title":"Front Cell Infect Microbiol"},{"issue":"9","key":"pone.0346930.ref080","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/j.bbamem.2014.04.015","article-title":"Peptide entry inhibitors of enveloped viruses: the importance of interfacial hydrophobicity","volume":"1838","author":"H Badani","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"pone.0346930.ref081","doi-asserted-by":"crossref","DOI":"10.1007\/s44370-024-00006-5","article-title":"A review on current status of antiviral peptides","volume":"2","author":"A Qureshi","year":"2025","journal-title":"Discov Viruses"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346930","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T17:29:33Z","timestamp":1775755773000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346930"}},"subtitle":[],"editor":[{"given":"Seth Agyei","family":"Domfeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":81,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0346930","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]}}}