Natural Snake Venom Inhibitors and their Pharmaceutical Uses: Challenges and Possibilities

Saavedra, Soledad L.; Ávila, Lucía; Giudicessi, Silvana L.; Alberício, Fernando; Camperi, Silvia A.; Cascone, Osvaldo; Ceron, Camila Martinez

doi:10.2174/1381612824666180223172854

Cited by 7 publications

(18 citation statements)

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“…Metalloproteases inhibitors have not yet been largely found in fungi (Dunaevsky et al ). On the other hand, non‐protein natural inhibitors were reported to have mechanisms such as hydrophobic interactions with aromatic residues present in the enzyme structure and complexation with metal ions (Saavedra et al ).…”

Section: Resultsmentioning

confidence: 99%

Lecanicillium aphanocladii: snake venom phospholipases A2 and proteases as tools to prospect enzymatic inhibitors

Cardoso

Trento

Reis

et al. 2019

Letters in Applied Microbiology

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Natural enzyme inhibitors have been widely described in literature because of its pharmacological and cosmetic applications. Fungi found in caves represent a promising source of bioactive substances that are still little explored scientifically. Thus, the present work evaluated the presence of enzymatic modulators in a filtrate obtained from the cultivation of the cave fungus Lecanicillium aphanocladii (Family: Cordycipitaceae). Snake venoms from Bothrops alternatus and Bothrops atrox were used as an enzymatic source for the induction of the phospholipase, proteolytic, thrombolytic, cytotoxic and coagulant activities. Compounds present in the fungal filtrate inhibited 50, 23·8, 26·6, 50·9 and 52·5% of the proteolytic, phospholipase, haemolytic, thrombolytic and coagulant activities respectively. The filtrate was not cytotoxic on erythrocytes, but induced partial dissolution of thrombi. Fungal enzyme inhibitors that have low or no toxicity and can be obtained on a large scale and at low cost are relevant in the medical‐scientific context. Therefore, the inhibition of phospholipases A2 and proteases observed in the present work highlights the potential of fungal metabolites for the development of drugs that can be used in the treatment of haemostasis and inflammation‐related disorders. Significance and Impact of the Study In this study, secondary metabolites synthesized by Lecanicillium aphanocladii, a fungus isolated from caves, demonstrated modulating action on proteases and phospholipases A2 present in snake venoms of the Bothrops genus, widely used as tools for the study of pathophysiology processes related to haemostasis and inflammation. The results suggest the possibility of future applications for these metabolites in the development of pharmaceuticals of medical‐scientific interest.

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Section: Resultsmentioning

confidence: 99%

Lecanicillium aphanocladii: snake venom phospholipases A2 and proteases as tools to prospect enzymatic inhibitors

Cardoso

Trento

Reis

et al. 2019

Letters in Applied Microbiology

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“…The effect of plant extracts in inhibiting snake venom enzymes is well documented (Carvalho et al 2013;Dar et al 2016;Coriolano de Oliveira et al 2016;Saavedra et al 2018;Amos Samkumar et al 2019;Nayak et al 2020). Compounds such as diterpene lactones, flavonoids, steroids, tannins and polyphenols found in plant extracts have been demonstrated to bind to venom enzymes (Carvalho et al 2013;Dar et al 2016), inhibiting them, as exemplified by docking studies (Sivakumar and Manikandan 2015;Amos Samkumar et al 2019).…”

Section: Introductionmentioning

confidence: 97%

Augmented rescue of macroglobulins by supplementation of anti-snake venom with methanolic extract of Andrographis paniculata in Naja naja envenomation

et al. 2022

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Proteins of the macroglobulin family are prime targets of venom enzymes in snake bite. A massive reduction in the active concentration of these multifunctional proteins in snake bite, makes the living system vulnerable to dysregulation. This study investigates the ability of Indian polyvalent anti-snake venom (ASV), methanolic extract of Andrographis paniculata (MAP) and their combination in rescuing human alpha 2-macroglobulin (A2MG) and its homologues in rat plasma, from inactivation by Naja naja (N.N) venom enzymes. In-vitro experiments were conducted with heparinized human plasma and in-vivo experiments with female Wistar rats. Along with appropriate controls, there were 3 test groups in in-vitro and 8 test groups in in-vivo experiments. The in-vitro test groups were exposed to N.N venom for zero, 30 or 90 min prior to incubation with ASV or MAP or reduced ASV supplemented with MAP and incubated for 16 h at 37 °C. Chymotrypsin-bound esterase (CTBE) activity of A2MG was estimated. Rats were administered the venom intramuscularly and treated with ASV/MAP/ASV + MAP. CTBE activity of macroglobulin homologues was measured on day 1, 7 and 14. Survival of animals was noted. In human plasma, addition of ASV or MAP or ASV + MAP prevented loss of A2MG activity maximally to the extent of 88–100% (p = 0.001). In rats, reduced concentration of ASV supplemented with MAP showed complete rescue of macroglobulin homologues and 90% survival. The compulsive evidence from this study, underscores the merits of using this multipronged strategy in rescuing the macroglobulins and improving survival in envenomation due to N.N.

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“…Swelling in the bite region is a common and major cause of serious complications for which negative pressure wound therapy has been shown effective. [2][3][4][5][6] However, a definitive treatment has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

“…Vitis vinifera seed extract (VVse) has been studied as an antivenom for snakebites and is useful for neutralization of various venom-induced activities. [3][4][5][6] It is reportedly effective in the treatment of bites by snakes from the Viperidae family and Russell's and hump-nosed vipers. [3][4][5][6] The local effects of viper bites can be treated with VVse through neutralization of the venom's edema-inducing and myonecrotic properties.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6] It is reportedly effective in the treatment of bites by snakes from the Viperidae family and Russell's and hump-nosed vipers. [3][4][5][6] The local effects of viper bites can be treated with VVse through neutralization of the venom's edema-inducing and myonecrotic properties. [3][4][5][6] VVse reportedly abolishes enzyme inhibition (hyaluronidase and proteolytic activities), neutralizes hemorrhage, and partially inhibits pro-coagulant activity attributed to viper venom.…”

Section: Introductionmentioning

confidence: 99%

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Treatment with Vitis vinifera extract for controlling ascites and local swelling in snakebites

In¹,

Oh²,

Min³

et al. 2023

Clin Exp Emerg Med

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Natural Snake Venom Inhibitors and their Pharmaceutical Uses: Challenges and Possibilities

Cited by 7 publications

References 0 publications

Lecanicillium aphanocladii: snake venom phospholipases A2 and proteases as tools to prospect enzymatic inhibitors

Lecanicillium aphanocladii: snake venom phospholipases A2 and proteases as tools to prospect enzymatic inhibitors

Augmented rescue of macroglobulins by supplementation of anti-snake venom with methanolic extract of Andrographis paniculata in Naja naja envenomation

Treatment with Vitis vinifera extract for controlling ascites and local swelling in snakebites

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