-Terphenyls as Anti-HSV-1/2 Agents from a Deep-Sea-Derived sp.

Guided by Global Natural Products Social molecular networking, two -terphenyl derivatives and one 4,5-diphenyl-2-pyrone analogue, peniterphenyls A-C (-), together with five known -terphenyl derivatives (-) and sulochrin (), were obtained from a deep-sea-derived sp. SCSIO41030. Their structures were elucidated using extensive NMR spectroscopic and HRESIMS data and by comparing the information with literature data. Peniterphenyl B () represented the first reported natural product possessing a 4,5-diphenyl-substituted 2-pyrone derivative. The -terphenyl derivatives displayed inhibitory activities against HSV-1/2 with EC values ranging from 1.4 ± 0.6 to 9.3 ± 3.7 μM in Vero cells, which showed that they possessed antiviral activities with low cytotoxicity, superior to the current clinical drug acyclovir (EC 3.6 ± 0.7 μM). Peniterphenyl A () inhibited HSV-1/2 virus entry into cells and may block HSV-1/2 infection through direct interaction with virus envelope glycoprotein D to interfere with virus adsorption and membrane fusion, and thus differs from the nucleoside analogues such as acyclovir. Our study indicated peniterphenyl A () could be a promising lead compound against HSV-1/2.