*1.11. Insects*

Although insects are the largest group within the arthropod phylum, and most of them are well studied due to their importance, there is always room for new research. Insects are known to create the biological foundation for most of the terrestrial ecosystems by pollinating plants, dispersing seeds, controlling populations of other organisms (including decomposing dead material to recycle nutrients) and being a major food source for other taxa. On the other hand, insects also spread diseases and can compromise a significant amount of food (grains, for example).

Among the notorious insects, there is the honeybee (*Apis mellifera*). There are reports of beekeeping as old as 10,000 years. Bee domestication started in Egypt 4500 years ago, when probably human accidents must have become more frequent, as well.

Bee stinging is mischievous: one single sting may provoke allergy and the subject may die from anaphylaxis. On the other hand, one may be stung several times and, in spite of intense pain and significant swelling, no significant harm occurs. However, when a few dozen bees sting, one may become envenomed. This event is not related to allergy and is a consequence of the bee toxins acting on the victim's body, especially in the kidneys.

The difference between poison and medicine is the dose, and apitherapy is a rather popular branch of alternative medicine which includes live bee acupuncture. Such a procedure may heal some, but is not free of risks at all! Adverse reactions to bee venom therapy are frequent. Constant exposure to the venom may lead to arthropathy, for example. In sensitized individuals, allergic reactions vary from mild, local swelling to severe systemic reactions, anaphylactic shock and even death. Yet, there are claimed cosmetic uses of the bee venom. Rumor has it that the Duchess of Cambridge has used bee venom to keep her skin looking flawless and even applied the secret ingredient to ensure a glowing complexion when she wed Prince William in 2011.

In a more practical context, a few groups have explored the possibility of developing an antiapilic serum, for treating those patients that have suffered multiple bee stings and have not suffered anaphylactic shock. Among those, authors from this group have successfully developed an efficient antiapilic serum that is currently under clinical trial (phase III). Further details can be found in the works of Ferreira Jr et al., 2010 [163], and Sciani et al., 2010 [164], who set the basis for the preclinical and clinical studies summarized by Barbosa et al., 2021 [165].

#### **2. Conclusions**

Animal venoms and toxins comprise a diverse repertoire of fascinating proteins, peptides and other bioactive molecules that have evolved through natural selection, driven by adaptive pressure and the survival of the fittest. Their biological role is—mainly predation and defense. Mankind—and its anthropocentric perspective of nature—have always tried to develop ways to use and study these venoms and toxins as pharmacological prototypes for the research and development of novel therapeutics. Such a quest has opened new venues to the identification of an unprecedented number of new molecules and/or biological effects.

According to our view, 'classic' toxinology (as we have termed the continuous study of snakes, scorpions and spiders) will lessen in the near future and the 'new' venoms and toxins will prevail, due to subject saturation. Research of unexplored—or neglected species of animals and their venoms and secretions should become dominant, since they contain a myriad of molecules displaying relevant biological effects on human illnesses, diseases, degenerative disorders, injuries, pain, tumors and infections (viral, bacterial and fungal), either as medicines or diagnostics tools.

Therefore, we consider that the currently reviewed literature on lizards, amphibians, and marine animals is just the beginning of a new thematic approach that we hope will become dominant in the following years. Such veiled potential currently hidden in the neglected animal venoms and toxins can set the instrumental and scientific basis for the

development of new molecules with innovative potential, which could shape a "new era" in toxinology.

**Author Contributions:** Conceptualization, G.R.C. and E.B.-N.; writing—original draft preparation, G.R.C., D.L.d.S., E.B.-N., H.V. and L.A.d.O.; writing—review and editing, E.B.-N. and H.V.; supervision, J.M.S. and D.C.P.; funding acquisition, J.M.S. and D.C.P. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant number 301974/2019-5, Financiadora de Estudos e Projetos (FINEP), grants number 01.12.0450.00 and 01.09.0278.04, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant number 19/19929-6. The APC was funded by Instituto Butantan.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.
