evaluation of (s)-10-hydroxycamptothecin inhibitor of herpes simplex type 1 identified from screening of a library of natural products

Background: herpes simplex virus type 1 (hsv-1) causes serious illness in humans, especially in newborns and immunocompromised hosts. public health requires the development of new, less toxic anti-hsv-1 drugs. objectives: this study aimed to evaluate the potential anti-herpesvirus activity of natural products in an extensive library of 133 compounds by examining viral titers and the number of viral plaques. methods: (s)-10-hydroxycamptothecin (10-hcpt) as an inhibitor against viral dna replication in the lowest concentration ranges from a set of natural products consisting of screening 133 compounds. each step of the viral replication cycle of hsv-1 on a549 cells was evaluated with different assays, including adsorption, penetration, time-of-addition assay, and quantitative polymerase chain reaction (pcr). the respective antiviral effects on hsv-1an95 infection were assessed in vitro. results: 10-hcpt was found to be a potent inhibitor of hsv-1 infection in the lowest concentration range from screening of a natural product library. the results showed that 10-hcpt significantly affects hsv-1 viral plaque formation inhibition, with a half maximal effective concentration (ec 50) of 0.07 μm. the time of addition assay suggested that 10-hcpt had a viral inhibitory effect when added 8 hours after infection. it was further confirmed by reducing the expression of late viral genes including glycoprotein (g) and viral protein (vp) (gb, gd, gh, vp1/2, and vp16) 4 hours after infection in the 10-hcpt treatment group compared to positive controls by quantitative real-time pcr. the western blotting results are inconsistent with other reported results. it showed that 10-hcpt did not affect gd and icp4 during hsv-1 infection, and 10-hcpt appeared to affect other genes in the immediate-early (ie) and late (l) steps. conclusions: 10-hcpt demonstrated anti-hsv activity on hsv-1. their dose-dependent antiviral activity showed that specific cellular components might mediate their function rather than cytotoxicity. this survey suggests a new outlook in exploring effective treatment options for hsv-1 infections.