Anti-Influenza A Viral Butenolide from Streptomyces sp. Smu03 Inhabiting the Intestine of Elephas maximus.

Fangfang Li,Xiaoling Zhang,Shaohua Wu,Sheng Fan,Jian He,Shengsheng Lu,Zhao Chen,Daiwei Chen,Guang Yang

doi:10.3390/v10070356

Abstract

Actinobacteria are a phylum of bacteria known for their potential in producing structurally diversified natural products that are always associated with a broad range of biological activities. In this paper, using an H5N1 pseudo-typed virus drug screening system combined with a bioassay guided purification approach, an antiviral butanolide (1) was identified from the culture broth of Streptomyces sp. SMU03, a bacterium isolated from the feces of Elephas maximus in Yunnan province, China. This compound displayed broad and potent activity against a panel of influenza viruses including H1N1 and H3N2 subtypes, as well as influenza B virus and clinical isolates with half maximal inhibitory concentration values (IC50) in the range of 0.29 to 12 µg/mL. In addition, 1 was also active against oseltamivir-resistant influenza virus strain of A/PR/8/34 with NA-H274Y mutation. Studies on the detailed modes of action suggested that 1 functioned by interfering with the fusogenic process of hemagglutinin (HA) of influenza A virus (IAV), thereby blocking the entry of virus into host cells. Furthermore, the anti-IAV activity of 1 was assessed with infected BALB/c mice, of which the appearance, weight, and histopathological changes in the infected lungs were significantly alleviated compared with the no-drug-treated group. Conclusively, these results provide evidence that natural products derived from microbes residing in animal intestines might be a good source for antiviral drug discovery.

Highlights

It is well documented that animal bodies, including human beings, are the reservoir of a wide variety of microbes, which play a critical role in the health and welfare of their hosts, and are associated with the etiology and pathogenesis of a large number of diseases [1]
A Butenolide Was Isolated from Streptomyces sp
Smu03 Residing in the Intestine of Elephas maximus

Summary

Introduction

It is well documented that animal bodies, including human beings, are the reservoir of a wide variety of microbes, which play a critical role in the health and welfare of their hosts, and are associated with the etiology and pathogenesis of a large number of diseases [1]. Among the microbes inhabiting the intestinal tract of animals, actinobacteria are a predominant group of bacteria and are known for their potential in producing functional secondary metabolites. These bioactive metabolites either inhibit the excessive growth of other microorganisms or improve the health of their animal host [2]. Viruses 2018, 10, 356 with their host over a long period of time and have been proven to be safe and effective by numerous in vivo “tests”, it is reasonably deduced that the bioactive metabolites isolated from bacteria inside the animal body might possess high potential for use as therapeutic agents, which prompted this investigation of the bioactive components from actinobacteria inhabiting the animal intestinal tract using the bioassay guided approach. There are two types of drugs available in clinics that target the viral neuraminidase (NA)

Methods

Results

Conclusion