Molecular Characterization of Kunitz-Type Protease Inhibitors from Blister Beetles (Coleoptera, Meloidae)

Abstract

Protease inhibitors are widely studied since the unrestricted activity of proteases can cause extensive organ lesions. In particular, elastase activity is involved in the pathophysiology of acute lung injury, for example during SARS-CoV-2 infection, while serine proteases and thrombin-like proteases are involved in the development and/or pathology of the nervous system. Natural protease inhibitors have the advantage to be reversible and with few side effects and thus are increasingly considered as new drugs. Kunitz-type protease inhibitors (KTPIs), reported in the venom of various organisms, such as wasps, spiders, scorpions, and snakes, have been studied for their potent anticoagulant activity and widespread protease inhibitor activity. Putative KTPI anticoagulants have been identified in transcriptomic resources obtained for two blister beetle species, Lydus trimaculatus and Mylabris variabilis. The KTPIs of L. trimaculatus and M. variabilis were characterized by combined transcriptomic and bioinformatics methodologies. The full-length mRNA sequences were divided on the base of the sequence of the active sites of the putative proteins. In silico protein structure analyses of each group of translational products show the biochemical features of the active sites and the potential protease targets. Validation of these genes is the first step for considering these molecules as new drugs for use in medicine.

Unveiling Novel Kunitz- and Waprin-Type Toxins in the Micrurus mipartitus Coral Snake Venom Gland: An In Silico Transcriptome Analysis

“…In nematodes, proteases regulate cyst development, a relevant stage in zoonosis [67]. Additionally, proteases participate in immune response and microbial infection in plants, insects, and fungi [68,69] and a plethora of bleeding and inflammation-related processes in animals, as well as in the nervous system, as voltage-gated ion channels are involved in critical processes related to nerve cells [70], making them versatile tools in many fields. Recently, several KSPI peptides from green mamba venom have been tested for effects on cyst development in polycystic kidney diseases via the inhibition of vasopressin type 2 receptor pathways [2,70].…”