Experimental antivenom against serine proteases from the Bothrops jararaca venom obtained in mice, and its comparison with the antibothropic serum from the Butantan Institute

Kuniyoshi, Alexandre Kazuo; Kodama, Roberto Tadashi; Cajado-Carvalho, Daniela; Iwai, Leo Kei; Kitano, Eduardo S.; Silva, Cristiane Castilho Fernandes da; Duzzi, Bruno; Silva, Wilmar Dias da; Portaro, Fernanda Calheta Vieira

doi:10.1016/j.toxicon.2019.09.001

Cited by 11 publications

(6 citation statements)

References 29 publications

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“…On the other hand, in assays with the B. jararaca venom, BAV was not able to inhibit the hydrolysis of the used substrate, even at higher doses (1:500, venom/antivenom). These results agree with the literature, since this failure of BAV to inhibit SVSPs present in Bothrops snake venoms has already been previously reported [19][20][21]. The four synthetic peptides that showed inhibition of Abz-Ser hydrolysis (CDR3 A, CDR3 C, CDR3 D and CDR3 E, Figure 5) showed superior efficacy when compared to BAV, being more effective in the assays with the B. jararaca venom.…”

Section: Comparison Of the Blocking Potential Of Bav And Synthetic Pe...supporting

confidence: 91%

“…While Bothrops atrox venom is not specifically included in the antigen pool used for the manufacture of BAV, it is utilized in cases of accidents caused by this species and all snakes of the Bothrops genus found in Brazil, due to the similarities in the composition of their venoms and the symptoms presented by the victims [16]. Even though BAV has saved countless lives [16,17], some studies have shown failures in its ability to neutralize certain components present in bothropic venoms, especially SVSPs [18][19][20][21], underscoring the need for its improvement. Furthermore, the development of new antivenoms is important and, in this scenario, monoclonal antibodies (mAbs) are raised as an alternative and promising tool to the currently used serum therapy [22].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Inhibitory Potential of Synthetic Peptides Homologous to CDR3 Regions of a Monoclonal Antibody against Bothropic Venom Serine Proteases

Saladini,

Magalhães-Junior,

da Silva

et al. 2024

IJMS

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Snakebite accidents, neglected tropical diseases per the WHO, pose a significant public health threat due to their severity and frequency. Envenomation by Bothrops genus snakes leads to severe manifestations due to proteolytic enzymes. While the antibothropic serum produced by the Butantan Institute saves lives, its efficacy is limited as it fails to neutralize certain serine proteases. Hence, developing new-generation antivenoms, like monoclonal antibodies, is crucial. This study aimed to explore the inhibitory potential of synthetic peptides homologous to the CDR3 regions of a monoclonal antibody targeting a snake venom thrombin-like enzyme (SVTLE) from B. atrox venom. Five synthetic peptides were studied, all stable against hydrolysis by venoms and serine proteases. Impressively, four peptides demonstrated uncompetitive SVTLE inhibition, with Ki values ranging from 10−6 to 10−7 M. These findings underscore the potential of short peptides homologous to CDR3 regions in blocking snake venom toxins, suggesting their promise as the basis for new-generation antivenoms. Thus, this study offers potential advancements in combatting snakebites, addressing a critical public health challenge in tropical and subtropical regions.

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Section: Comparison Of the Blocking Potential Of Bav And Synthetic Pe...supporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Evaluation of the Inhibitory Potential of Synthetic Peptides Homologous to CDR3 Regions of a Monoclonal Antibody against Bothropic Venom Serine Proteases

Saladini,

Magalhães-Junior,

da Silva

et al. 2024

IJMS

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“…The presence of immunodominant venom components has been shown in other snake venoms. Kuniyoshi et al [ 31 ] demonstrated that the commercial anti-Bothropic antivenom, produced by the Butantan Institute using an immunization pool composed of five different Bothrops spp. venoms, was very efficient in recognizing the bothropic SVMPs but did not react against the SVSPs, indicating a lack of specific antibodies against the serine proteases in the serum.…”

Section: Discussionmentioning

confidence: 99%

“…Megale et al [ 34 ] isolated and characterized a fibrinogenolytic and kinin-releasing SVSP directly related to the hypotension observed in envenomation patients. Kuniyoshi et al [ 31 ] were able to immunize animals with a pool of SVSPs isolated from Bothropic venom and develop specific anti-SVSP antibodies. Godoi et al [ 35 ] isolated the less immunogenic SVMPs from the B. arietans venom and developed anti-SVMP antibodies capable of neutralizing the local hemorrhagic effects induced by that venom.…”

Section: Discussionmentioning

confidence: 99%

Comparing Traditional and Toxin-Oriented Approaches towards Antivenom Production against Bitis arietans Snake Venom

Guidolin,

de Godoi,

Megale

et al. 2023

Toxins

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Accidents with snakes are responsible for about 32,000 deaths annually in sub-Saharan Africa, caused mostly by snakes from the genus Bitis, in particular Bitis arietans. B. arietans venom is composed of a complex mixture of toxins, mainly metalloproteases, serine proteases, phospholipases, lectins, and disintegrins. In this work, we compared two approaches to anti-B. arietans antivenom production: immunization with crude snake venom (“traditional approach”) and immunization with selected key toxins isolated from the snake venom (“toxin oriented” approach). Fractions from B. arietans venom were isolated by size exclusion chromatography. Crude venom and samples containing serine proteases or metalloproteases were selected for the immunization of BALB/c mice. Anti-B. arietans and anti-serine proteases plasmas showed a similar recognition profile and higher titers and affinity than the anti-metalloproteases plasma. Cross-recognition of other Bitis venoms was observed, but with low intensity. Although the plasma of all experimental groups inhibited the enzymatic activity of B. arietans venom in vitro, in vivo protection was not achieved. Our results have shown limitations in both approaches considered. Based on this, we proposed a model of polyclonal, species-specific, monovalent antivenoms that could be used as a base to produce customizable polyvalent sera for use in sub-Saharan Africa.

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“…The venom of the Micrurus ibiboboca snake also immersed within SBA-15 MSNs facilitated the modulation and stimulation of antibodies for the development of possible vaccines [ 32 ]. This type of nanosystem has been widely used, primarily to obtain antivenom serum [ 95 ].…”

Section: Nanosystems and Nanocarriersmentioning

confidence: 99%

Nanobiotechnology with Therapeutically Relevant Macromolecules from Animal Venoms: Venoms, Toxins, and Antimicrobial Peptides

et al. 2022

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Some diseases of uncontrolled proliferation such as cancer, as well as infectious diseases, are the main cause of death in the world, and their causative agents have rapidly developed resistance to the various existing treatments, making them even more dangerous. Thereby, the discovery of new therapeutic agents is a challenge promoted by the World Health Organization (WHO). Biomacromolecules, isolated or synthesized from a natural template, have therapeutic properties which have not yet been fully studied, and represent an unexplored potential in the search for new drugs. These substances, starting from conglomerates of proteins and other substances such as animal venoms, or from minor substances such as bioactive peptides, help fight diseases or counteract harmful effects. The high effectiveness of these biomacromolecules makes them promising substances for obtaining new drugs; however, their low bioavailability or stability in biological systems is a challenge to be overcome in the coming years with the help of nanotechnology. The objective of this review article is to describe the relationship between the structure and function of biomacromolecules of animal origin that have applications already described using nanotechnology and targeted delivery.

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Experimental antivenom against serine proteases from the Bothrops jararaca venom obtained in mice, and its comparison with the antibothropic serum from the Butantan Institute

Cited by 11 publications

References 29 publications

Evaluation of the Inhibitory Potential of Synthetic Peptides Homologous to CDR3 Regions of a Monoclonal Antibody against Bothropic Venom Serine Proteases

Evaluation of the Inhibitory Potential of Synthetic Peptides Homologous to CDR3 Regions of a Monoclonal Antibody against Bothropic Venom Serine Proteases

Comparing Traditional and Toxin-Oriented Approaches towards Antivenom Production against Bitis arietans Snake Venom

Nanobiotechnology with Therapeutically Relevant Macromolecules from Animal Venoms: Venoms, Toxins, and Antimicrobial Peptides

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