<i>p</i>-Terphenyls as Anti-HSV-1/2 Agents from a Deep-Sea-Derived <i>Penicillium</i> sp.
Weihao Chen, Jiawen Zhang, Xin Qi, Kai Zhao, Xiaoyan Pang, Xiuping Lin, Shengrong Liao, Bin Yang, Xuefeng Zhou, Shuwen Liu, Junfeng Wang, Xingang Yao, Yonghong Liu
Abstract
Guided by Global Natural Products Social molecular networking, two p-terphenyl derivatives and one 4,5-diphenyl-2-pyrone analogue, peniterphenyls A–C (1–3), together with five known p-terphenyl derivatives (4–8) and sulochrin (9), were obtained from a deep-sea-derived Penicillium sp. SCSIO41030. Their structures were elucidated using extensive NMR spectroscopic and HRESIMS data and by comparing the information with literature data. Peniterphenyl B (2) represented the first reported natural product possessing a 4,5-diphenyl-substituted 2-pyrone derivative. The p-terphenyl derivatives displayed inhibitory activities against HSV-1/2 with EC50 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 (EC50 3.6 ± 0.7 μM). Peniterphenyl A (1) 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 (1) could be a promising lead compound against HSV-1/2.