Anti-Influenza A Viral Butenolide from Streptomyces sp. Smu03 Inhabiting the Intestine of Elephas maximus
Fangfang Li,
Daiwei Chen,
Shengsheng Lu,
Guang Yang,
Xiaoling Zhang,
Zhao Chen,
Sheng Fan,
Shaohua Wu,
Jian He
Affiliations
Fangfang Li
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
Daiwei Chen
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
Shengsheng Lu
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
Guang Yang
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
Xiaoling Zhang
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
Zhao Chen
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
Sheng Fan
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
Shaohua Wu
Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan Institute of Microbiology, School of Life Sciences, Yunnan University, Kunming 650091, China
Jian He
Group of peptides and natural products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, China
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.
