Molecular Recognition and Immunopharmacological Implications of Serratiopeptidase Targeting Snake Venom Bradykinin-Potentiating Peptides

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  Molecular Recognition and Immunopharmacological Implications of Serratiopeptidase Targeting Snake Venom Bradykinin-Potentiating Peptides Abstract Purpose Bradykinin-potentiating peptides (BPPs), found in snake venom, are known to modulate cardiovascular functions, but their susceptibility to enzymatic degradation remains poorly understood. Methods Models were generated using AlphaFold-Colab for five small BPPs (< 9 amino acids) that did not have experimentally solved structures, and those BPPs which had reliable predictions of structure (pLDDT > 80) were used for docking studies. Protein-peptide docking experiments were done using HADDOCK for studying the interaction between wild-type (WT) and mutant serratiopeptidase with BPPs. After selecting the best complex, simulation of the complex was done using molecular dynamics (MD) simulations for 100 ns and binding energy determination using MM/PBSA analysis. For checking the mechanical stability of the protein-peptide complexes...

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

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Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Abstract

Enterovirus 71 (EV71), a typical representative of unenveloped RNA viruses, is the main pathogenic factor responsible for hand, foot, and mouth disease (HFMD) in infants. This disease seriously threatens the health and lives of humans worldwide, especially in the Asia–Pacific region. Numerous animal antimicrobial peptides have been found with protective functions against viruses, bacteria, fungi, parasites, and other pathogens, but there are few studies on the use of scorpion-derived antimicrobial peptides against unenveloped viruses. Here, we investigated the antiviral activities of scorpion venom antimicrobial peptide BmKn2 and five derivatives, finding that BmKn2 and its derivative BmKn2-T5 exhibit a significant inhibitory effect on EV71. Although both peptides exhibit characteristics typical of amphiphilic α-helices in terms of their secondary structure, BmKn2-T5 displayed lower cellular cytotoxicity than BmKn2. BmKn2-T5 was further found to inhibit EV71 in a dose-dependent manner in vitro. Moreover, time-of-drug-addition experiments showed that BmKn2-T5 mainly restricts EV71, but not its virion or replication, at the early stages of the viral cycle. Interestingly, BmKn2-T5 was also found to suppress the replication of the enveloped viruses DENV, ZIKV, and HSV-1 in the early stages of the viral cycle, which suggests they may share a common early infection step with EV71. Together, the results of our study identified that the scorpion-derived antimicrobial peptide BmKn2-T5 showed valuable antiviral properties against EV71 in vitro, but also against other enveloped viruses, making it a potential new candidate therapeutic molecule.

Xia, Zhiqiang, Huijuan Wang, Weilie Chen, Aili Wang, and Zhijian Cao. 2024. "Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro" Biomolecules 14, no. 5: 545. https://doi.org/10.3390/biom14050545