title: Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell's Viper Venom.
abstract: Russell's viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs) are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs): RVV-X and Daborhagin were purified from Myanmar Russell's viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS) approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs) were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell's viper envenomation.
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. khinthanyee@gmail.com.
authors.forename: Khin Than
authors.initials: KT
authors.lastname: Yee
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK. morganpitts@hotmail.co.uk.
authors.forename: Morgan
authors.initials: M
authors.lastname: Pitts
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. kpsppto@ku.ac.th.
authors.forename: Pumipat
authors.initials: P
authors.lastname: Tongyoo
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. rojnuckarinp@gmail.com.
authors.forename: Ponlapat
authors.initials: P
authors.lastname: Rojnuckarin
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK. Mwilk@liverpool.ac.uk.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Wilkinson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002052:Myanmar; D017840:Daboia; D059467:Transcriptome; D014757:Viper Venoms / Q000201:enzymology* / Q000494:pharmacology*
chemical_list: D000997:Antivenins; D014757:Viper Venoms; D008666:Metalloendopeptidases; C033858:russellysin
keywords: Russell’s viper; snake venom metalloproteinase inhibitors; snake venom metalloproteinases; viper venom