55 / 2021-10-10 14:41:35

p-Terphenyls as Anti-HSV-1/2 Agents from a Deep-sea Derived Penicillium sp. SCSIO41030

Terphenyl;,Anti-HSV;,Penicillium sp,Deep-Sea Derived Fungus

Herpes simplex virus (classified as type I and type II, HSV-1/2), was accountable for encephalitis or genital herpes, which caused serious public health threat.¹ And the emergence of adverse side effects and drug-resistance due to the extensive use of antivirals have indicated the need for new anti-HSV drugs.² Marine microorganisms represent a promising source of new bioactive secondary metabolites for drug discovery in recent years. In our ongoing search for novel bioactive compounds from deep-sea fungi,³ a strain Penicillium sp. SCSIO41030 was studied.

Guided by Global Natural Products Social molecular networking, two new p-terphenyl derivatives and one novel 4,5-diphenyl-2-pyrone analogue, peniterphenyls A−C (1‒3) were obtained from liquid medium of the strain. Their structures were elucidated using extensive NMR spectroscopic and HRESIMS data. Peniterphenyl A (1) displayed inhibitory activities against HSV-1/2 with EC₅₀ values of 1.4 ± 0.6 and 2.2 ± 0.7 μM in Vero cells, which showed that it possessed antiviral activities with low cytotoxicity and superior to the current clinical drug acyclovir (EC₅₀ 3.6 ± 0.7 μM). Further investigations revealed that 1 inhibited HSV-1/2 entry into Vero cells and may block HSV-1/2 infection through direct interaction with virus envelope glycoprotein D (gD protein) to interfere with virus adsorption and membrane fusion, and thus differs from the nucleoside analogues such as acyclovir. Our study indicated peniterphenyl A (1) could be a promising lead compound against HSV-1/2.

References:

1. Widener, R. W., Whitley, R. J. Herpes Simplex Virus. Handb. Clin. Neurol. 2014, 123, 251–263.

2. Hassan, S. T. S., Masarčíková, R., Berchová, K. Bioactive natural products with anti-herpes simplex virus properties. J. Pharm. Pharmacol. 2015, 67 (10), 1325–1336.

3. Chen, S. T., Wang, J. F., Lin, X. P., et al. Chrysamides A–C, three dimeric nitrophenyl trans-epoxyamides produced by the deep-sea-derived fungus Penicillium chrysogenum SCSIO41001. Org. Lett. 2016, 18 (15), 3650–3653.