A novel RRGW derived peptide is a promising inhibitor of BoNT/A

Wantong Ma; Lulu Wang; Xiangmin Tan; Xin Wang; Chunyan Yang; Yu Wang; Ziye Liu; Bo Liu; Hai Zhu; Dejuan Zhi; Dongsheng Wang

doi:10.1080/14756366.2023.2203878

A novel RRGW derived peptide is a promising inhibitor of BoNT/A

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2203878. doi: 10.1080/14756366.2023.2203878.

Authors

Wantong Ma¹, Lulu Wang¹, Xiangmin Tan¹, Xin Wang¹, Chunyan Yang¹, Yu Wang¹, Ziye Liu¹, Bo Liu¹, Hai Zhu¹, Dejuan Zhi^{1

2}, Dongsheng Wang^{1

2

3}

Affiliations

¹ School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.
² Frontiers Science Center for Rare Isotopes, Lanzhou University, Lanzhou, P.R. China.
³ State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou, P.R. China.

Abstract

Clostridium botulinum neurotoxin type A (BoNT/A) is one of the most potent biotoxins ever known. Its entry into neurons could block vesicle exocytosis to abolish the release of neurotransmitters from nerve terminals, thus leading to muscle paralysis. Although there are so many peptides, antibodies and chemical compounds claimed to have anti-toxin activity, no drug is available in the clinical application except equine antitoxin serum. In the present work, a short peptide inhibitor RRGW of BoNT/A was firstly identified by computer-aided ligand-receptor binding simulation, then an RRGW derived peptide was rational designed based on the fragment of SNAP-25 (141-206 aa). Proteolytic assay showed that the anti-toxin activity of the RRGW derived peptide was much higher than that of RRGW. Digit abduction score assay demonstrated that the derived peptide delayed BoNT/A-induced muscle paralysis at a lower concentration by 20-fold than RRGW. The results supported that RRGW derived peptide can be a potential BoNT/A inhibitor candidate for further treating botulism.

Keywords: Botulinum neurotoxins A; Derived peptide; Dynamics simulations; Inhibitors.

MeSH terms

Animals
Botulinum Toxins, Type A* / pharmacology
Botulism* / drug therapy
Horses
Paralysis
Peptides / pharmacology

Substances

Botulinum Toxins, Type A
peptide I
Peptides

Grants and funding

This work was supported by National Natural Science Foundation of China [Grant No. 82073825]; the Key Project of Gansu Province Science and Technology, China [Grant No. 22ZD6FA053]; Fundamental Research Funds for the Central Universities [Grant No. lzujbky-2021-sp32] and Medical Innovation and Development Project of Lanzhou University [Grant No. lzuyxcx-2022–197].