Generation of truncated derivatives through in silico enzymatic digest of peptide GV30 target MRSA both in vitro and in vivo

Methicillin-resistant Staphylococcus aureus (MRSA) causing serious hospital-acquired infections and skin infections has become a superbug in clinical treatment. Although the clinical treatment of MRSA is con-tinuously improving, due to its unceasing global spread, MRSA has produced much heated discussion and focused study, therefore suggesting an urgent task to find new antibacterial drugs to combat this issue. Antimicrobial peptides (AMPs) are used as the last-resort drugs for treating multidrug-resistant bacterial infections, but their utilisation is still limited due to their low stability and often strong toxicity. Here, we evaluated the structure and the bioactivity of an AMP, GV30, derived from the frog skin secre-tions of Hylarana guentheri, and designed seven truncated derivatives based on the presence of cleavage sites for trypsin using an online proteomic bioinformatic resource PeptideCutter tool. We investigated the anti-MRSA effect, toxicity and salt-and serum-resistance of these peptides. Interestingly, the structure-activity relationship revealed that removing Rana box loop could significantly improve the bactericidal speed on MRSA. Among these derivatives, GV21 (GVIFNALKGVAKTVAAQLLKK-NH2), because of its faster antibacterial effect, lower toxicity, and retains the good antibacterial activity and stability of the parent peptide, is considered to become a new potential antibacterial candidate against MRSA. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

Automated summary

MRSA, a superbug causing serious hospital-acquired and skin infections, has prompted the urgent need for new antibacterial drugs. This study evaluated an AMP, GV30, derived from frog skin secretions, and designed seven truncated derivatives, with GV21 showing faster antibacterial effect, lower toxicity, and overall promising potential as a new antibacterial candidate against MRSA.