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.
Highlights
The synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective Snake venom metalloproteinases (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
Russell’s viper (Daboia russelii) is a medically important snake, variants of which are distributed throughout East and Southeast Asia
The proteins resolved into two peaks and the first peak (Q1) exhibited caseinolytic activity (Figure 2a)
Summary
Russell’s viper (Daboia russelii) is a medically important snake, variants of which are distributed throughout East and Southeast Asia. A Russell’s viper bite has a 60% morbidity rate and the fatality rate is 8.2% in Myanmar [1]. The cause of death includes shock, massive bleeding and renal failure. Snake venom metalloproteinases (SVMPs) play a major role in the local and systemic clinical manifestations: blistering, necrosis and bleeding from the fang marks and incoagulable blood, thrombocytopenia, spontaneous systemic bleeding, hypotension, increased permeability and reduced urine output [2]. Russell’s viper antivenoms are available, their efficacy in reversal tissue damage, such as acute renal failure, is limited [3].
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