Synthetic surfactin analogues have improved anti-PEDV properties

Lvfeng Yuan; Shuai Zhang; Jie Peng; Yuchen Li; Qian Yang

doi:10.1371/journal.pone.0215227

Synthetic surfactin analogues have improved anti-PEDV properties

PLoS One. 2019 Apr 11;14(4):e0215227. doi: 10.1371/journal.pone.0215227. eCollection 2019.

Authors

Lvfeng Yuan¹, Shuai Zhang¹, Jie Peng², Yuchen Li¹, Qian Yang¹

Affiliations

¹ MOE Joint International Research Laboratory of Animal Health and Food Safety, College of veterinary medicine, Nanjing Agricultural University, Jiangsu, PR China.
² College of veterinary medicine, Gansu Agricultural University, Gansu, PR China.

Abstract

Surfactin has antiviral activity against various enveloped viruses by inhibiting viral membrane fusion. However, the potential utility of surfactin as an antiviral drug is limited by its cytotoxicity. In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The main goal of our study was to develop a safer drug; a surfactin analogue with high anti-PEDV activity and low hemolytic activity. Compared with surfactin, one of the analogues we developed, SLP5, has lower hemolytic activity, with the same antiviral activity. The selectivity index of SLP5 is 52, while the SI for surfactin is 4, in other words, the safe and effective concentration range of SLP5 is 12 times greater than that of surfactin. Like surfactin, SLP5 has a direct antiviral effect on PEDV. Structurally, SLP5 is a linear lipopeptide with three carboxyl groups. Surfactin derivatives similar to SLP5 could be obtained by lactone bond hydrolyzation of surfactin, as well as total synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Chlorocebus aethiops
Drug Design
Hemolysis / drug effects
Lipopeptides / chemical synthesis
Lipopeptides / chemistry
Lipopeptides / pharmacology*
Micelles
Molecular Structure
Peptides, Cyclic / chemical synthesis
Peptides, Cyclic / chemistry
Peptides, Cyclic / pharmacology*
Porcine epidemic diarrhea virus / drug effects*
Porcine epidemic diarrhea virus / pathogenicity
Porcine epidemic diarrhea virus / physiology
Sus scrofa
Vero Cells
Virus Internalization / drug effects

Substances

Antiviral Agents
Lipopeptides
Micelles
Peptides, Cyclic

Grants and funding

This work was supported by National Natural Science Foundation of China, 31772777 (http://www.nsfc.gov.cn/english/site_1/) and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) to QY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.