Antiviral Activities of Compounds Isolated from <i>Pinus densiflora</i> (Pine Tree) against the Influenza A Virus
2020
Thi Kim Quy Ha | Ba Wool Lee | Ngoc Hieu Nguyen | Hyo Moon Cho | Thamizhiniyan Venkatesan | Thi Phuong Doan | Eunhee Kim | Won Keun Oh
<i>Pinus densiflora</i> was screened in an ongoing project to discover anti-influenza candidates from natural products. An extensive phytochemical investigation provided 26 compounds, including two new megastigmane glycosides (<b>1</b> and <b>2</b>), 21 diterpenoids (<b>3–23</b>), and three flavonoids (<b>24–26</b>). The chemical structures were elucidated by a series of chemical reactions, including modified Mosher’s analysis and various spectroscopic measurements such as LC/MS and 1D- and 2D-NMR. The anti-influenza A activities of all isolates were screened by cytopathic effect (CPE) inhibition assays and neuraminidase (NA) inhibition assays. Ten candidates were selected, and detailed mechanistic studies were performed by various assays, such as Western blot, immunofluorescence, real-time PCR and flow cytometry. Compound <b>5</b> exerted its antiviral activity not by direct neutralizing virion surface proteins, such as HA, but by inhibiting the expression of viral mRNA. In contrast, compound <b>24</b> showed NA inhibitory activity in a noncompetitive manner with little effect on viral mRNA expression. Interestingly, both compounds <b>5</b> and <b>24</b> were shown to inhibit nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Taken together, these results provide not only the chemical profiling of <i>P. densiflora</i> but also anti-influenza A candidates.
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