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.

The Russell’s viper (Daboia siamensis) is a medically important venomous snake in Myanmar. Next-generation sequencing (NGS) shows potential to investigate the venom complexity, giving deeper insights into snakebite pathogenesis and possible drug discoveries. mRNA from venom gland tissue was extracted and sequenced on the Illumina HiSeq platform and de novo assembled by Trinity. The candidate toxin genes were identified via the Venomix pipeline. Protein sequences of identified toxin candidates were compared with the previously described venom proteins using Clustal Omega to assess the positional homology among candidates. Candidate venom transcripts were classified into 23 toxin gene families including 53 unique full-length transcripts. C-type lectins (CTLs) were the most highly expressed, followed by Kunitz-type serine protease inhibitors, disintegrins and Bradykinin potentiating peptide/C-type natriuretic peptide (BPP-CNP) precursors. Phospholipase A₂, snake venom serine proteases, metalloproteinases, vascular endothelial growth factors, L-amino acid oxidases and cysteine-rich secretory proteins were under-represented within the transcriptomes. Several isoforms of transcripts which had not been previously reported in this species were discovered and described. Myanmar Russell’s viper venom glands displayed unique sex-specific transcriptome profiles which were correlated with clinical manifestation of envenoming. Our results show that NGS is a useful tool to comprehensively examine understudied venomous snakes.

Objectives. To estimate the frequency of Metabolic Syndrome (MS in Myanmar obese children and to determine the risk factors associated with MS in obese children comparing with normal weight children. Methodology. A cross-sectional study was conducted to compare the risk factors for metabolic syndrome between normal and obese children by using the pediatric definition for metabolic syndrome [International Diabetes Federation (IDF), 2007]. Twenty-three obese children (BMI, ≥ 97 th percentile) and 23 normal weight children (BMI, < 85 th percentile) aged 5-12 years were included in the study. Blood pressure, body weight, height, waist circumference (WC), fasting triglycerides, HDL-cholesterol, total cholesterol and glucose concentrations were determined. Results. Based on the IDF pediatric criteria, 9 obese children (39.1%) had metabolic syndrome while no normal weight child had metabolic syndrome. Ten (43.5%) normal weight children and 3 (13.0%) obese children had at least one risk factor for the metabolic syndrome. Central obesity (WC ³ 90 th percentile for age and sex), the most common risk factor, was observed in 25 children (54.4% of the total population). Conclusion. This study highlights the need for early recognition of risk factors for metabolic syndrome in all children to halt the progression of type 2 diabetes and cardiovascular diseases (CVD) in later life.

Snakebite is a neglected public health issue, with many scientific and medical issues to be solved. Cobras are among the most common venomous snakes in Myanmar and are responsible for a considerable number of severe snakebite envenoming. There are three species of cobra (Naja kaouthia, Naja mandalayensis and Ophiophagus hannah) in Myanmar. The study aims to characterize the N. kaouthia and N. mandalayensis venoms and to investigate the efficacy of anti-cobra antivenom (BPI) against the two venoms. Protein components and fibrinogenolytic activity were determined by SDS-PAGE. Enzymatic activities for PLA₂, protease and acetylcholinesterase were determined by spectrophotometric method. Anticoagulant activity was determined by recalcification time of citrated human plasma. Myotoxicity, necrotizing activity, median lethal dose (LD₅₀) and median effective dose (ED₅₀) were determined by WHO recommended methods. The SDS-PAGE displayed the proteins and enzymes containing in two venoms were different. N. kaouthia venom exhibited more in PLA₂, acetylcholinesterase, anticoagulant, fibrinogenolytic and necrotizing activities than N. mandalayensis venom. N. mandalayensis venom had more protease activity and myotoxicity than N. kaouthia venom. The median lethal dose (LD₅₀) of N. kaouthia and N. mandalayensis venom was 4.33 μg/mouse and 5.04 μg/mouse respectively. Both venoms induced fibrinogen Aα chain degradation in 30 min (N. kaouthia) and in 6 h (N. mandalayensis). The same median effective dose (ED₅₀) (19.56 μg/mouse) showed that anti-NK antivenom can neutralize against lethal effect of N. mandalayensis venom. It can also neutralize the protease activity, anticoagulant activity and fibrinogenolytic activity of both venoms. Immunodiffusion and immunoblotting studies showed that the antivenom recognized its homologous venom (N. kaouthia) and cross-reacted against the heterologous venom (N. mandalayensis). The anti-NK antivenom is suitable to use for N. mandalayensis bite if monospecific antivenom is not available.

Russell’s viper (Daboia siamensis) is a medically important snake in Myanmar due to its high morbidity and mortality. The genome of Myanmar Russell’s viper had not been sequenced until recently. Hence, RNA sequencing has been used to predict genes that encode this snake’s toxins. This can lead to deeper insights into the pathogenesis of envenoming and potential drug discovery. Venom glands were dissected from four adult D. siamensis specimens (two males and two females) provided by a local Myanmar snake farm. The mRNA was extracted and sequenced on the Illumina HiSeq platform, then assembled de novo using the Trinity software. Candidate toxin genes were identified using the Venomix pipeline, and their expression levels were calculated using RSEM software. The identified toxin candidates were aligned with previously described venom proteins using Clustal Omega. Candidate venom transcripts were classified into 23 toxin gene families, which included 53 unique transcripts identified as full-length sequences. Among them, 28 full-length sequences represented the eight newly identified toxin gene families in D. siamensis, including neprilysin (2), cystatin (5), waprin (1), vipericidin (1), veficolin (1), endothelial lipases (9), vespryn (ohanin) (8), and three-finger toxins (1). Their expression levels were found to be moderate to low (TPM = 1.49 to 213.37). The majority of the toxin candidates resembled typical elapid toxins, which usually exhibit neurotoxic activities and tissue damage. A smaller proportion of candidate toxin transcripts were predicted to display antimicrobial activity and anti-metastatic effects. Our results suggest their functional activities. They should be studied further for potential therapeutic applications.