Inhibitory effect of various recombinant corn trypsin inhibitor variants against trypsin

Background and objective: Trypsin is best known for playing a role in enteric digestion, among the most commonly examined serine proteases. Trypsin is expressed extra-pancreatically by a number of cancer types (for instance, Ovarian cancer), and it is thought that both in vivo and in vitro carcinogenesis are facilitated by trypsin. A new study suggests that trypsin overexpression may promote Coronavirus transmission. In this investigation, several corn trypsin inhibitor (CTI) variants will be expressed and purified, and their trypsin inhibitory action will be assessed. Methods: CTI was cloned and expressed, and then different variants of rCTI were expressed and assessed for their ability to inhibit trypsin enzyme activity. Results: The Arg34Ala amino acid substitution negated all inhibitory activity, whereas Gly32Trp, Trp22Ala reduced inhibitory activity by considerable degrees, respectively six-fold and seven-fold; Arg27Ala, Glu39Ala, Arg42Ala, Arg27Ala-Arg42Ala didn't affect inhibitory activity either. Conclusion: CTI's central inhibition loop is critical for binding trypsin, and the data confirm that Arg34, Trp22, and Gly32 of the loop are involved. It is possible to design new, specific, and safe drug candidates based on the residues for the treatment of ovarian cancer using this framework. This study can also serve as a starting point for designing drugs that reduce the symptoms of COVID-19 caused by trypsin-induced cytokinestorm. Keywords: CTI; Mutation, Inhibition; Trypsin; Ovarian cancer; COVID-19.