Antiviral Activity of Oridonin Against Herpes Simplex Virus Type 1.

Abstract

In search of new potent treatment of herpes simplex keratitis (HSK), inhibitory effect of oridonin (Ori) on herpes simplex virus type 1 (HSV-1) was validated by experiments. For evaluating inhibitory effect of oridonin on herpes simplex virus type 1, a series of in-vivo and in-vitro studies were carried out. Mouse HSV-1 infection model was used in the in-vivo experiments. Experimental mice were classified infivedifferentgroups: Mock (mock-infected), HSV-1+ DMSO, HSV-1+ Ori, HSV-1+ ACV, combined Ori and ACV+HSV-1. Corneas of Mock, HSV-1+ DMSO, HSV-1+ Ori group were sent formRNA-sequencing after 3 days post infection (dpi). The expression of virus and host-related genes was evaluated by quantitative real-time polymerase chain reaction (qPCR). Vero cells HSV-1 infection models were used in the in-vitro experiments. The application of ACV, Oridonin alone or a combination of both could alleviate HSV-1 severity and inhibit HSV-1 virus replication in C57BL/6 mice models. qPCR showed that compared with mock group, the expression of interleukin-6 (il-6), interleukin-1α (il-1α), and Tumor-necrosis factor-alpha (tnf-α) was up-regulated in DMSO+HSV-1 group and suppressed in other three group. Moreover, the expression of nod-like receptor protein (nlrp3), caspase 1 and interleukin-1β (il-1β) were depressed in the oridonin-treated group. Oridonin significantly inhibits HSV-1 replication, HSV-1 related gene expression, and the production of progeny HSV-1 viruses in vitro. Besides, oridonin affect the replication phase but not HSV-1 entry or penetration and cannot inactivate HSV-1. Oridonin alleviates herpes simplex keratitis infection in mouse, which may be attributed to inhibition of the NLRP3-inflammasome-IL-1β pathway. Our study illustrates that Oridonin has potential promise for application in treating HSK and other diseases caused by HSV-1 infection.