Antiviral Activity And Its Mechanism Of LCVN Against HSV-1 Drug-resistant Strains

Backgroud: Herpes simplex virus type 1(HSV-1)is a double-stranded DNA Virus,which human infection rate is very high.The main infection site of HSV-1 is oral mucosa.After initial infection,HSV-1 is transported to the trigeminal ganglia to establish a lifelong latent infection and can be reactivated by stimulus.Acyclovir(ACV)is usually used in the treatment of HSV-1 infection.This usually leads to the emergence of acyclovir resistant strains,especially immunosuppressed patients with long-term preventive treatment.Purpose: Standard strain(HSV-1 F),ACV-resistant strains(HSV-1 153 / HSV-1 BLUE / HSV-1 106)were used to investigate the antiviral activity of Cyanovirin-N(CVN)and its derivatives(LCVN / mPEG10K-ALD-LCVN).Moreover,antiviral mechanism of LCVN was studied.Contents and Results: The cytotoxicity of CVN,LCVN and mPEG10K-ALD-LCVN were assessed using MTT test.The median lethal concentration(TC50)were 1.456±0.340 ?M,1.747±0.097 ?M,9.48±1.403 ?M respectively;The comprehensive antivirus effect of LCVN on three drug-resistant strains(HSV-1 153 / HSV-1 BLUE / HSV-1 106)and standard strain(HSV-1 F)were detected by the plaque reduction assay.LCVN and mPEG10K-ALD-LCVN completely inhibit viral infection at the concentration of 0.1 ?M and 2 ?M respectively.The antiviral activity of CVN,LCVN and mPEG10K-ALD-LCVN was stronger than acyclovir significantly at low micromolar.Antiviral mechanism of LCVN was assessed through plaque reduction assay.The effect of prevention,the effect of preventing viral attachment and penetration were modest whereas the therapeutic effect was noticeable.RT-QPCR and Western-blot were used to detect the transcription of viral RNA and synthesis of viral protein.The results show that LCVN cannot inhibit the immediate early gene transcription and protein synthesis,but can significantly inhibit the late gene transcription and protein synthesis.Significance: It is easy for the nucleoside analogue to develop drug-resistant strains following long period of treatment.LCVN inhibit HSV-1 and its drug-resistant strains though multiple mechanisms.Thus,LCVN is an effective drug for HSV-1 and its drug-resistant strains.