Anti-HSV-1 Activity Of Gallic Tannins And The Quantitative Structure-Activity Relationship Study

Objective:To evaluate anti-HSV-1 activities of a series of extracts from nanyao, and use of computer-aided drug design approach to study the quantitative structure-activity relationship of the gallic tannins as HSV-1 inhibitors, to provide theoretical basis for the development of novel antiviral drugs.Methods:1) Cytotoxic effects of the extracts from nanyao on Vero cells were determined by MTT (3-{4,5-dimethylthiazol-2-y}-2-5-diphenytetrazolium bromide) method. Anti-viral activities of the extracts were examined by cytopathic effect (CPE) observation and plaque reduction assay (PRA).2) Based on the previous work of our team, combined with the literatures which reported anti-HSV-1 activities of gallic tannins, the structure-activity database of gallic tannins was established.3) 2D-QSAR model was established by using HQSAR method, to explore the molecular fragments which were closely related to the bio-activity of the compounds.4) 3D-QSAR model was established by using CoMFA and CoMSIA methods, to investigate the relationship between different force fields of the compounds and its bio-activities.Results:1) Some of the extracts from nanyao have showed anti-HSV-1 activity, especially extracts from the fruits of Phyllanthus emblica (SML-P14-E1), fruits of Eucalyptus maideni (SML-P18-E2, SML-P18-E3) and leaves of Psidium guajava L. (SML-P44). All of these samples'TI values are higher than 15. 2) The 2D-QSAR model showed that the cross-validated coefficient q2 was 0.808, the non cross-validation R2 was 0.900, the standard deviation SE was 0.146, component was 3, best length was 151, which means the 2D-QSAR model have good predictive ability.3) 3D-QSAR model, which was established by CoMFA method, showed that the cross-validated coefficient q2 was 0.370, the non cross-validation R2 was 0.951, the standard deviation SE was 0.102, and component was 3. In this model, the q2 was smaller than 0.4, which indicated the predictive ability of this model is not good enough. Accordingly, the CoMFA model was rejected.4) 3D-QSAR model which was build using CoMSIA method showed that the cross-validated coefficient q2 was 0.660, the non cross-validation R2 was 0.943, the standard deviation SE was 0.116, and component was 4. In this model, the q2 was higher than 0.6, demonstrated this model have good predictive ability. In this CoMSIA model, evidence showed the hydrophobic field, hydrogen acceptor and electrostatic field of gallic tannins have great relevant with the anti-HSV-1 activities.Conclusion:1) There are some active constituents among the extracts for further research, such as Phyllanthus emblica (SML-P14-E1), Eucalyptus maideni (SML-P18-E2, SML-P18-E3) and Psidium guajava L. (SML-P44).2) Evaluation of the gallic tannins as HSV-1 inhibitor structure-activity relationship revealed the 2D and 3D-QSAR models can be used in this research.3) According to the models, galloyl played an important role on antiviral activity. Meanwhile, hydrophobic field was very essential. Hydrophobic groups can be helpful to increase the anti-HSV-1 activity of gallic tannins.