scholarly journals Anticoagulant Activity of Naja nigricollis Venom Is Mediated by Phospholipase A2 Toxins and Inhibited by Varespladib

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 302
Author(s):  
Taline D. Kazandjian ◽  
Arif Arrahman ◽  
Kristina B. M. Still ◽  
Govert W. Somsen ◽  
Freek J. Vonk ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Anticoagulant Activity ◽  
West African ◽  
Snake Venoms ◽  
The West ◽  
Coagulation Assays ◽  
Venom Toxins ◽  
African Black ◽  
Snake Venom Metalloproteinase ◽  
Species Specific

Bites from elapid snakes typically result in neurotoxic symptoms in snakebite victims. Neurotoxins are, therefore, often the focus of research relating to understanding the pathogenesis of elapid bites. However, recent evidence suggests that some elapid snake venoms contain anticoagulant toxins which may help neurotoxic components spread more rapidly. This study examines the effects of venom from the West African black-necked spitting cobra (Naja nigricollis) on blood coagulation and identifies potential coagulopathic toxins. An integrated RPLC-MS methodology, coupled with nanofractionation, was first used to separate venom components, followed by MS, proteomics and coagulopathic bioassays. Coagulation assays were performed on both crude and nanofractionated N. nigricollis venom toxins as well as PLA2s and 3FTx purified from the venom. Assays were then repeated with the addition of either the phospholipase A2 inhibitor varespladib or the snake venom metalloproteinase inhibitor marimastat to assess whether either toxin inhibitor is capable of neutralizing coagulopathic venom activity. Subsequent proteomic analysis was performed on nanofractionated bioactive venom toxins using tryptic digestion followed by nanoLC-MS/MS measurements, which were then identified using Swiss-Prot and species-specific database searches. Varespladib, but not marimastat, was found to significantly reduce the anticoagulant activity of N. nigricollis venom and MS and proteomics analyses confirmed that the anticoagulant venom components mostly consisted of PLA2 proteins. We, therefore, conclude that PLA2s are the most likely candidates responsible for anticoagulant effects stimulated by N. nigricollis venom.

scholarly journals Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 297 ◽  
Author(s):  
Chunfang Xie ◽  
Laura-Oana Albulescu ◽  
Mátyás A. Bittenbinder ◽  
Govert W. Somsen ◽  
Freek J. Vonk ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Small Molecule ◽  
Snake Venom ◽  
Small Molecule Inhibitors ◽  
Drug Repurposing ◽  
Proteomics Data ◽  
Snake Venoms ◽  
Analytical Technique ◽  
Venom Toxins ◽  
Snake Venom Metalloproteinase

Animal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A2 (varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found in Viperinae snake venoms. The venoms of Echis carinatus, Echis ocellatus, Daboia russelii and Bitis arietans, which are known for their potent haemotoxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A2-inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combinations of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming.

Effects of salinity on strontium:calcium ratios in the otoliths of the West African black-chinned tilapia Sarotherodon melanotheron in a hypersaline estuary

2006 ◽  
Vol 77 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Khady Diouf ◽  
Jacques Panfili ◽  
Maylis Labonne ◽  
Catherine Aliaume ◽  
Javier Tomás ◽  
...  
Keyword(s):  
West African ◽  
The West ◽  
African Black ◽  
Sarotherodon Melanotheron

scholarly journals Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 165 ◽  
Author(s):  
Chunfang Xie ◽  
Laura-Oana Albulescu ◽  
Kristina B. M. Still ◽  
Julien Slagboom ◽  
Yumei Zhao ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Snake Venom ◽  
Snake Venoms ◽  
Venom Toxins ◽  
Inhibitory Molecule ◽  
Coagulation Assay ◽  
Potential Clinical Utility ◽  
Bothrops Asper ◽  
Echis Carinatus ◽  
Deinagkistrodon Acutus

Phospholipase A2 (PLA2) enzymes are important toxins found in many snake venoms, and they can exhibit a variety of toxic activities including causing hemolysis and/or anticoagulation. In this study, the inhibiting effects of the small molecule PLA2 inhibitor varespladib on snake venom PLA2s was investigated by nanofractionation analytics, which combined chromatography, mass spectrometry (MS), and bioassays. The venoms of the medically important snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus, Echis ocellatus, and Oxyuranus scutellatus were separated by liquid chromatography (LC) followed by nanofractionation and interrogation of the fractions by a coagulation assay and a PLA2 assay. Next, we assessed the ability of varespladib to inhibit the activity of enzymatic PLA2s and the coagulopathic toxicities induced by fractionated snake venom toxins, and identified these bioactive venom toxins and those inhibited by varespladib by using parallel recorded LC-MS data and proteomics analysis. We demonstrated here that varespladib was not only capable of inhibiting the PLA2 activities of hemotoxic snake venoms, but can also effectively neutralize the coagulopathic toxicities (most profoundly anticoagulation) induced by venom toxins. While varespladib effectively inhibited PLA2 toxins responsible for anticoagulant effects, we also found some evidence that this inhibitory molecule can partially abrogate procoagulant venom effects caused by different toxin families. These findings further emphasize the potential clinical utility of varespladib in mitigating the toxic effects of certain snakebites.

scholarly journals Effect of Intercropping Beans with Maize and Botanical Extract on Fall Armyworm (Spodoptera frugiperda) Infestation

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Clovis Bessong Tanyi ◽  
Raymond Ndip Nkongho ◽  
Justin Nambangia Okolle ◽  
Aaron Suh Tening ◽  
Christopher Ngosong
Keyword(s):  
Spodoptera Frugiperda ◽  
Cropping Systems ◽  
Fall Armyworm ◽  
Black Pepper ◽  
West African ◽  
Control Measures ◽  
The West ◽  
Piper Guineense ◽  
Synthetic Insecticide ◽  
African Black

African farmers are currently grappling with potential control measures for the invasive fall armyworm (FAW) (Spodoptera frugiperda), which has recently emerged as an important economic pest that is ravaging maize fields across the continent. We evaluated the efficacy of the West African black pepper extract and beans intercropping systems as viable FAW control measures and the implication on maize yields. The experiment comprised five treatments (control-no input, dwarf beans intercrop, climbing beans intercrop, West African black pepper extract, and insecticide) with three replications each. FAW severity was assessed at three to seven weeks after planting (WAP), while maize infestation was assessed at seven WAP. FAW severity increased significantly (P<0.05) across WAP for the control and dwarf beans intercrop, with the highest at four and six WAP, respectively. FAW severity also differed (P<0.05) significantly across treatments at four to seven WAP, with the lowest recorded in the extract of West African black pepper (Piper guineense) and the highest in control treatments. Maize infestation ranged from 13 to 93%, with the lowest in the West African black pepper extract and synthetic insecticide, followed by both dwarf and climbing beans intercrops and then the control. The maize yield determined at physiological maturity ranged from 2.2 to 6.3 t ha−1 across treatments and differed significantly, with the highest in the West African black pepper extract and synthetic insecticide, followed by both the dwarf and climbing beans intercrops, as compared to the control. Overall, the West African black pepper extract and beans push cropping systems demonstrated efficacy as viable sustainable alternative control measures for the invasive fall armyworm in maize fields.

scholarly journals Neutralizing effects of small molecule inhibitors and metal chelators on coagulopathic Viperinae snake venom toxins

2020 ◽  
Author(s):  
Chunfang Xie ◽  
Laura Albulescu ◽  
Matyas A Bittenbinder ◽  
Govert Somsen ◽  
Freek Vonk ◽  
...  
Keyword(s):  
Small Molecule ◽  
Snake Venom ◽  
Small Molecule Inhibitors ◽  
Drug Repurposing ◽  
Phospholipase A ◽  
Proteomics Data ◽  
Snake Venoms ◽  
Analytical Technique ◽  
Venom Toxins ◽  
Snake Venom Metalloproteinase

AbstractAnimal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A2 (varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found in Viperinae snake venoms. The venoms of Echis carinatus, Echis ocellatus, Daboia russelii and Bitis arietans, which are known for their potent coagulopathic toxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A2-inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combination of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming.

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