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

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.

Evaluation of the effects of Loxosceles intermedia’s venom in zebrafish

“…Said diversity is associated to the spider’s defense strategies against different predators, as well as prey capture and digestion [32] . In the context of loxoscelism, the crucial role of toxins such as phospholipases, hyaluronidases and metalloproteases has been studied in mammal envenomation [33] , [34] . Low mass toxins, such as knottins, also present in Loxosceles venom, have shown to affect different species of arthropods, thus showing an insecticidal properties [35] .…”

Generalized edema and necrosis of the lower lip

“…Loxosceles antivenom is the only specific treatment against loxoscelism and its use is the standard recommendation in several countries, including Brazil (Gremski et al, 2021; Miranda et al, 2021). After intravenous administration of the antivenom, there was complete regression of the submandibular edema and the patient remained in the hospital for 8 days, until he was able to eat.…”