Antiviral Activity and its Mechanism of LCVN Against HSV-1 Acyclovir-resistant Strains

Aim A standard strain of HSV-1 (strain F) and Acyclovir(ACV)-resistant strains HSV-1 (strain 153/BLUE/106) were used to investigate the antiviral activity of Cyanovirin-N (CVN) and its derivatives (LCVN, mPEG10K-ALD-LCVN). Moreover, antiviral mode and mechanism of antiviral of LCVN was studied. Experimental HSV-1 (strain F) was maintained in our laboratory and propagated in Vero cells. HSV-1 (strain 153/BLUE/106) resistant strains were isolated from children with herpes labial in Guangzhou Children's Hospital. Purified recombinant CVN, LCVN and thePEGylated product 10 K PEGALD-LCVN were prepared in-house by a processmodified as reported previously.Vero cells were maintained in our laboratory and grown in DMEM medium supplemented with 10% FBS, 100 U/mL penicillin and 100 microg/mL streptomycin. Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CVN and itsderivatives on HSV-1 in Vero cells. The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR). Result and discussion The results showed that CVN, LCVN and mPEG10K-ALD-LCVN had a low cytotoxicity on Vero cells with a median lethal concentration (TC50) of 1.456±0.340 microM1.747±0.097 microM 9.48±1.403 microM respectively; LCVN and mPEG10K-ALD-LCVN completely inhibit viral infection at the concentration of 0.1 microM and 2 microM respectively. The antiviral activity of CVN, LCVN and mPEG10K-ALD-LCVN were stronger than acyclovir significantly at Low micromolar. The effect of inhibiting viral attachment and penetration of LCVN were modest whereas thetreatment after virus infection was noticeable. The results showed that LCVN cannot inhibit the transcription of immediate early gene (UL54), but it can significantly inhibit transcription of the late gene (UL27), thereby inhibiting viral proliferation. Conclusion It is easy for the nucleoside analogue to develop drug-resistant strains following long period of treatment, whereas LCVN can inhibit HSV-1 and its ACV-resistant strains though multiple mechanisms. Thus, LCVN is an effective drug for HSV-1 and its ACV-resistant strains.