2. Academic Validation
  3. Spiromastilactones: A new class of influenza virus inhibitors from deep-sea fungus

Spiromastilactones: A new class of influenza virus inhibitors from deep-sea fungus

  • Eur J Med Chem. 2016 Jan 27:108:229-244. doi: 10.1016/j.ejmech.2015.09.037.
Siwen Niu 1,  Longlong Si 2,  Dong Liu 2,  Andrew Zhou 2,  Ziwei Zhang 2,  Zongze Shao 3,  Shaomeng Wang 4,  Lihe Zhang 2,  Demin Zhou 5,  Wenhan Lin 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China; Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, SOA, Xiamen, 361005, PR China.
  • 2 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China.
  • 3 Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, SOA, Xiamen, 361005, PR China.
  • 4 Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, United States.
  • 5 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China. Electronic address: deminzhou@bjmu.edu.cn.
  • 6 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China. Electronic address: whlin@bjmu.edu.cn.
PMID: 26686929 DOI: 10.1016/j.ejmech.2015.09.037
Abstract

A new class of phenolic lactones with trivial names of spiromastilactones A-M (1-13) was isolated from a deep-sea derived Spiromastix sp. fungus. Their structures featured by various chlorination at aromatic rings were determined on the basis of extensive spectroscopic analyses. An Antiviral assay revealed that most of the tested compounds exert inhibitory activity against WSN Influenza Virus with low cytotoxicity, while the structure-activity relationships were discussed. Spiromastilactone D (4), a 5'-chloro-2'-methoxy substituted analogue, displayed the most potent to inhibit a panel of influenza A and B viruses in addition to drug-resistant clinical isolates. Mechanistic investigation resulted in that compound 4 bonded to hemagglutinin protein (HA), potentially at the spherical head, and disrupted the HA-sialic acid receptor interaction, that is essential for the attachment and entry of all influenza viruses. In addition, compound 4 also showed inhibitory effect toward viral genome replication via targeting viral RNP complex. The synergistic effects of 4 on both viral entry and replication assumed it to be a promising lead for the development of a new influenza inhibitor.

Keywords

Antiviral effect; Influenza virus; Marine-derived fungus; Mechanistic investigation; Spiromastilactones; Spiromastix sp..

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