‘Partitagin’ a hemorrhagic metalloprotease from Hippasa partita spider venom: Role in tissue necrosis

Nagaraju, S.; Girish, K. S.; Fox, James W.; Kemparaju, K.

doi:10.1016/j.biochi.2007.04.005

Cited by 26 publications

(15 citation statements)

References 37 publications

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“…To determine the effect of compound 5d on caseinolytic activity of EC venom, substrate gel assay was carried out as described by Nagaraju et al [29]. Briefly, casein was co-polymerized with a final concentration of 0.2% in to native-PAGE (10%).…”

Section: Methodsmentioning

confidence: 99%

Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

et al. 2014

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The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues are synthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC) venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological study further conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and bothropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound 5d could be a potent agent in viper bite management.

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Section: Methodsmentioning

confidence: 99%

Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

et al. 2014

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“…A similar inhibition of proteolytic activity on fibrinogen has also been observed in vitro for EDTA (concentration of 2 mM) and 1,10-phenanthroline (concentration of 3 mM) on Loxosceles intermedia (Brown spider) venom [134]. Finally, both EDTA and 1,10-phenanthroline, at a concentration of 5 mM each, have been shown to specifically inhibit metalloproteases isolated from Hippasa partita venoms [138], whilst EDTA (1 mM) alone has proven to block metalloproteases from Parawixia bistriata (Araneidae genus) [137]. …”

Section: Toxin Inhibition By Small Moleculesmentioning

confidence: 55%

Biotechnological Trends in Spider and Scorpion Antivenom Development

Laustsen

Solà

Jappe

et al. 2016

Toxins

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Spiders and scorpions are notorious for their fearful dispositions and their ability to inject venom into prey and predators, causing symptoms such as necrosis, paralysis, and excruciating pain. Information on venom composition and the toxins present in these species is growing due to an interest in using bioactive toxins from spiders and scorpions for drug discovery purposes and for solving crystal structures of membrane-embedded receptors. Additionally, the identification and isolation of a myriad of spider and scorpion toxins has allowed research within next generation antivenoms to progress at an increasingly faster pace. In this review, the current knowledge of spider and scorpion venoms is presented, followed by a discussion of all published biotechnological efforts within development of spider and scorpion antitoxins based on small molecules, antibodies and fragments thereof, and next generation immunization strategies. The increasing number of discovery and development efforts within this field may point towards an upcoming transition from serum-based antivenoms towards therapeutic solutions based on modern biotechnology.

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“…Preparation of venom glands extract and isolation of Partitagin was performed according to Nagaraju et al [5]. Briefly, adult female spiders were anesthetized using chloroform inhalation, dissected and a pair of venom glands was collected into ice cold phosphate-buffered saline (PBS).…”

Section: Preparation Of Venom Glands Extract and Isolation Of Partitaginmentioning

confidence: 99%

“…It degraded the extracellular matrix (ECM) molecules such as type IV collagen and fibronectin. Partitagin was devoid of myotoxicity as it did not affect myocytes, whereas caused extensive myonecrosis as it degraded the structural proteins present in the ECM of muscle tissue [5]. Despite its dermonecrotic and myonecrotic effects, Partitagin has not been studied for its effect on fibrinogen, fibrin and platelet aggregation.…”

Section: Introductionmentioning

confidence: 99%

‘Partitagin’, a unique β, γ-fibrinogenase that inhibits platelet aggregation from Hippasa partita spider venom

Nagaraju

Kemparaju²

2011

Blood Coagulation &Amp; Fibrinolysis

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Partitagin, a Zn-containing hemorrhagic metalloprotease from Hippasa partita spider venom gland extract has been purified and studied for its dermonecrotic and myonecrotic effects. In the present study, Partitagin has been studied for its effect on fibrinogen, fibrin and platelet aggregation. Partitagin incubated with fibrinogen preferentially cleaved Bβ chain and later γ-chain upon prolonged incubation period (16 h). Partitagin upon incubation with fibrin degraded γ-dimer chain. Partitagin inhibited collagen-triggered platelet aggregation. The proteolytic activity of Partitagin was inhibited by serum α2-macroglobulin (α2-M). This is the first report describing β, γ-fibrinogenase having inhibitory effect on platelet aggregation.

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‘Partitagin’ a hemorrhagic metalloprotease from Hippasa partita spider venom: Role in tissue necrosis

Cited by 26 publications

References 37 publications

Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

Biotechnological Trends in Spider and Scorpion Antivenom Development

‘Partitagin’, a unique β, γ-fibrinogenase that inhibits platelet aggregation from Hippasa partita spider venom

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