Citrus bioflavonoid, hesperetin, as inhibitor of two thrombin-like snake venom serine proteases isolated from Crotalus simus

Santos, Roney Vander Dos; Villalta-Romero, Fabián; Stanisić, Danijela; Borro, Luiz; Neshich, Goran; Tasić, Ljubica

doi:10.1016/j.toxicon.2018.01.005

Cited by 22 publications

(10 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Additionally, HSD and HST have been reported to inhibit intracellular replication of CHIKV [29]. Vander dos Santos and collaborators described inhibition of serine proteases by HST, isolated from snake venom [39], thereby demonstrating possible inhibitory potential of these molecules against different proteases.…”

Section: Introductionmentioning

confidence: 99%

In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases

et al. 2021

View full text Add to dashboard Cite

The potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genus Alphavirus), dengue virus (DENV, genus Flavivirus), and zika virus (ZIKV, genus Flavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection. The results described in our study demonstrate the inhibitory potential of two flavonoids derived from citrus plants: Hesperetin (HST) against NS2B/NS3pro of ZIKV and nsP2pro of CHIKV and, Hesperidin (HSD) against nsP2pro of CHIKV. The flavonoids are noncompetitive inhibitors and the determined IC50 values are in low µM range for HST against ZIKV NS2B/NS3pro (12.6 ± 1.3 µM) and against CHIKV nsP2pro (2.5 ± 0.4 µM). The IC50 for HSD against CHIKV nsP2pro was 7.1 ± 1.1 µM. The calculated ligand efficiencies for HST were > 0.3, which reflect its potential to be used as a lead compound. Docking and molecular dynamics simulations display the effect of HST and HSD on the protease 3D models of CHIKV and ZIKV. Conformational changes after ligand binding and their effect on the substrate-binding pocket of the proteases were investigated. Additionally, MTT assays demonstrated a very low cytotoxicity of both the molecules. Based on our results, we assume that HST comprise a chemical structure that serves as a starting point molecule to develop a potent inhibitor to combat CHIKV and ZIKV co-infections by inhibiting the virus proteases.

show abstract

Section: Introductionmentioning

confidence: 99%

In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases

et al. 2021

View full text Add to dashboard Cite

show abstract

“…For instance, the compound “AIPLAI” was isolated from the methanolic extract of the leaves of the plant Azadirachta indica inhibited venom PLA 2 in a dose-dependent manner, with reductions in activity ranging from 10% to 60% [ 33 ]. Flavonoids from citrus fruit extracts, particularly hesperetin, inhibit two SVSPs expressed by Crotalus simus [ 45 ]. Macrolobin A, derived from Pentaclethra macroloba extracts, reduced PI-SVMP and PIII-SVMP-induced proteolytic activity by up to 90% and 80%, respectively [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

A First Look at the Inhibitory Potential of Urospatha sagittifolia (Araceae) Ethanolic Extract for Bothrops atrox Snakebite Envenomation

Palacios

Sacoto-Torres

Hernández-Altamirano

et al. 2022

Toxins

View full text Add to dashboard Cite

Bothrops atrox snakebites are a relevant problem in the Amazon basin. In this biodiverse region, the ethnomedicinal approach plays an important role as an alternative to antivenom therapy. Urospatha sagittifolia (Araceae) is a plant used for this purpose; however, its neutralizing properties have not been scientifically accessed. To fill this gap, we investigated the ability of U. sagittifolia to modulate the catalytic activity of Bothrops atrox venom, and their toxic consequences, such as local damage and lethality. The venom profile of B. atrox was assessed by chromatography and electrophoresis. Inhibition of the three main enzymatic and medically important toxins from the venom was evaluated using synthetic substrates and quantified by chromogenic activity assays. Additionally, the neutralization of lethality, hemorrhage and edema were investigated by in vivo assays. The possible interactions between venom proteins and plant molecules were visualized by polyacrylamide gel electrophoresis. Finally, the phytochemical constituents present in the ethanolic extract were determined by qualitative and quantitative analyses. The ethanolic extract reduced the activity of the three main enzymes of venom target, achieving ranges from 19% to 81% of inhibition. Our in vivo venom neuralizations assays showed a significant inhibition of edema (38.72%) and hemorrhage (42.90%). Additionally, lethality was remarkably counteracted. The highest extract ratio evaluated had a 75% survival rate. Our data support the biomedical value of U. sagittifolia as a source of natural enzyme inhibitors able to neutralize catalytically active B. atrox venom toxins and their toxic effects.

show abstract

“…Several studies demonstrated the inhibition by phenolic compounds on other classes of toxins such as metalloproteases and serine proteases. [37,38] Enzymes belonging to the trypsin family such as snake venom metalloproteases (SVMPs), zinc-dependent enzymes, and snake venom serine proteases (SVSPs) are common in snakes from the families Viperidae and Colubridae. [21,39] These enzymes act in the degradation of substrates such as immunoglobulin, components of the cell membrane, and plasma proteins (eg, coagulation cascade).…”

Section: Discussionmentioning

confidence: 99%

Catechin and epicatechin as an adjuvant in the therapy of hemostasis disorders induced by snake venoms

César

Trento

Konig

et al. 2020

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Snake toxins, such as phospholipases A 2 and proteases, are used as research tools to evaluate biological activities and to understand physiopathological processes of natural compounds better. In the present study, the phenolic compounds catechin and epicatechin were incubated with snake venoms to evaluate their inhibition against different substrates. Catechin and epicatechin exerted inhibitions between 20% and 95% on the activity of phospholipases A 2 present in the venom of Bothrops alternatus. In the hemolytic activity, catechin exerted inhibitions between 20% and 25% in all proportions evaluated on the B. jararacussu venom, whereas epicatechin inhibited 20% of the venom activity. Coagulation induced by B. atrox and B. jararacussu venoms was significantly inhibited by catechin and epicatechin, where the time for coagulation was two to three times higher after previous incubation of the venoms with the compounds. The most significant inhibitions for the proteolytic activity on casein were 17% and 27%, respectively, by both compounds. Catechin inhibited serine protease activity induced by B. atrox venom by 64% and epicatechin by 65%. Regarding B. atrox-induced thrombolysis, catechin exerted 40% inhibition and epicatechin around 30%. The fibrinogen proteolysis was completely inhibited by catechin acting on the B. atrox venom in the proportion of 1:1 and by epicatechin on B. jararacussu venom. Catechin and epicatechin showed promising inhibitory action on proteases and phospholipases A 2. Therefore, these compounds can be explored as an adjuvant for serum therapy or pharmaceutical purposes, once they act on homologous enzymes that are present in humans.

show abstract

Citrus bioflavonoid, hesperetin, as inhibitor of two thrombin-like snake venom serine proteases isolated from Crotalus simus

Cited by 22 publications

References 27 publications

In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases

In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases

A First Look at the Inhibitory Potential of Urospatha sagittifolia (Araceae) Ethanolic Extract for Bothrops atrox Snakebite Envenomation

Catechin and epicatechin as an adjuvant in the therapy of hemostasis disorders induced by snake venoms

Contact Info

Product

Resources

About