**9. Concluding Remarks**

The hemorrhagic syndrome is one of the most serious complications in patients who have contact with the *L. obliqua* caterpillar bristles. After the burst of accidents with hemorrhagic manifestations in 1989 in the states of south and southeast Brazil, many efforts were put into finding a solution to the public health problem that reached alarming proportions. Fortunately, the treatment with ALS produced at the Butantan Institute drastically reduced the consequences of the envenoming. All these efforts have resulted in substantial knowledge about the pathophysiology of the envenoming and the toxins contained in the venom.

Over the years, research has diversified, addressing not only the hematological alterations of the venom but also the role of toxins in each observed manifestation (Table 2). New molecules identified demonstrate peculiarities, such as hemolin and lipocalin structures with enzymatic or cellular activities that have never previously been reported for these types of proteins. This opened new perspectives for the use of those molecules in several applications, as diagnostic agents, for example, to detect dysprothrombinemias, as in the case of Lopap, which resulted in several patents granted, or as therapeutic agents for use in defibrinogenating and antithrombotic therapy (Lopap) or for promoting wound healing (Lopap- and Losac-derived peptides) (Table 3).

The creation of multidisciplinary research centers specialized in the study of animal envenomation and animal toxins promoted the interaction of partnerships with the pharmaceutical industry, e.g., CENTD, taking the study of molecules derived from venoms

and toxins to another level, favoring the development and innovation of new molecules. High-throughput screening technologies for new drugs or target discovery are extensively used at CENTD using toxin-derived peptides as tools for identifying new targets for inflammatory diseases.

Therefore, it is clear that the efforts of distinct groups at Butantan Institute have not only contributed to accumulated knowledge about the toxinology of *Lonomia*, but also created the basis for the development of ALS, essential in reducing the deaths due to lononism, and prompted the institute to develop innovative initiatives with toxinderived peptides.

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

**Funding:** This research was funded by "Grant 2015/50040-4, São Paulo Research Foundation and GlaxoSmithKline", "Grant 2020/13139-0, São Paulo Research Foundation and GlaxoSmithKline", and Grant number 2013/07467-1 (FAPESP-CETICs). A.M.C.-T. is a recipient of CNPq-PQ grant number 303197/2017-0 and Fundação Butantan-PQ grants. R.N.G. is a recipient of FAPESP grant number 2018/20469-7. A.M.A is a recipient of FAPESP grant number 2018/10937-3.

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

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data presented in this study are available on request from the corresponding author.

**Acknowledgments:** The authors thank Rafaella Lafraia for research on SINAN.

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

#### **References**


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