Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs.

Luiza Helena Gremski,Pedro Henrique De Caires Schluga,Silvio Sanches Veiga,Ana Carolina Martins Wille,Hanna Câmara Da Justa,João Carlos Minozzo,Fernando Hitomi Matsubara,Nayanne Louise Costacurta Polli,Bruno Cesar Antunes,Andrea Senff-Ribeiro

doi:10.3389/fmolb.2021.706704

Luiza Helena Gremski, Pedro Henrique De Caires Schluga + Show 8 more

Open Access

https://doi.org/10.3389/fmolb.2021.706704

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Abstract

Brown spider (genus Loxosceles) venoms are mainly composed of protein toxins used for predation and defense. Bites of these spiders most commonly produce a local dermonecrotic lesion with gravitational spread, edema and hemorrhage, which together are defined as cutaneous loxoscelism. Systemic loxoscelism, such as hematological abnormalities and renal injury, are less frequent but more lethal. Some Loxosceles venom toxins have already been isolated and extensively studied, such as phospholipases D (PLDs), which have been recombinantly expressed and were proven to reproduce toxic activities associated to the whole venom. PLDs have a notable potential to be engineered and converted in non-toxic antigens to produce a new generation of antivenoms or vaccines. PLDs also can serve as tools to discover inhibitors to be used as therapeutic agents. Other Loxosceles toxins have been identified and functionally characterized, such as hyaluronidases, allergen factor, serpin, TCTP and knottins (ICK peptides). All these toxins were produced as recombinant molecules and are biologically active molecules that can be used as tools for the potential development of chemical candidates to tackle many medical and biological threats, acting, for instance, as antitumoral, insecticides, analgesic, antigens for allergy tests and biochemical reagents for cell studies. In addition, these recombinant toxins may be useful to develop a rational therapy for loxoscelism. This review summarizes the main candidates for the development of drugs and biotechnological inputs that have been described in Brown spider venoms.

Highlights

Brown spiders are well-adapted arthropods with more than 150 species distributed in all continents
A serine protease inhibitor from the Serpin superfamily was described in a Loxosceles venom and, its role as a toxin remains to be elucidated, the biological activities of this inhibitor indicate a great potential for drug development (Graeff et al, 2019)
Comparative analyses between the protection of animals immunized with recombinant active or inactive isoforms of L. laeta PLDs showed that both protocols reduced the development of dermonecrotic lesions induced by L. laeta venom at similar levels, reinforcing that the antigenic potential of these enzymes is not related to their activity (Catalán et al, 2011)

Summary

Introduction

Brown spiders are well-adapted arthropods with more than 150 species distributed in all continents A serine protease inhibitor from the Serpin superfamily was described in a Loxosceles venom and, its role as a toxin remains to be elucidated, the biological activities of this inhibitor indicate a great potential for drug development (Graeff et al, 2019).

Results

Conclusion