Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues.Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that typically causes mucocutaneous lesions in oral, perioral, and other mucosal sites in the body (58). The virus commonly uses the oropharyngeal mucosa as a port of entry, and after primary infection, establishes a lifelong latent state in the host's trigeminal ganglia sensory neurons. Sporadic recurring infections occur when HSV-1 is reactivated by various stimuli, such as sunlight, immunosuppression, menstruation, fever, or stress (23). Although primary or reactivated HSV-1 infections can be subclinical or manifested by mild and self-limited diseases, severe cases of this viral infection may lead to complications such as keratoconjunctivitis, meningitis, and encephalitis (3, 5). Importantly, corneal HSV-1 infection can lead to stromal keratitis, which remains one of the leading causes of blindness in developing countries (37). More aggressive diseases due to HSV-1 are common in immunocompromised individuals (3,5,23). To date, no treatment has been identified that eradicates or resolves latent infections by this ubiquitous pathogen.HSV-1 viral entry into cells is initiated by interaction of viral envelope glycoproteins (gB and gC) with host cell surface proteoglycans (PGs) conjugated to glycosaminoglycans (GAGs) containing...

BackgroundWe previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry.ResultsExtensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses.ConclusionsCHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.

In this paper, a study and analysis of a distance measure method based on single vision with the aid of a laser pen is proposed. In the method, a camera and a laser pen are used as measurement device. By comparing the lightness of the pixels, the laser point projected on the object is found out in the image. Then an orthogonal triangle using the distance between laser point and CCD center as one edge is set up. And Pythagorean Theorem is applied to calculate the distance between camera and measured object. Experiments in different lightness are carried out and encouraging results are obtained which prove that the device has nice measuring performance in appropriate lightness.