Study On Anti-HSV-1 Activity And Mechanism Of Aspergillipeptide D Extracted From The Secondary Metabolites Of Marine Fungi

Objective: Screening out the antiviral lead compound with new structure and mechanism from marine microorganic secondary metabolites and discussing its antiviral activity and molecular mechanism initially,lay the foundation for the exploitation of novel antiviral marine drugs.Methods: The antiviral polypeptide compound Aspergillipeptide D with novel structure was screened out by CPE assay and its cytotoxicity was detected by MTT assay.To use plaque reduction assay detected the therapeutic activities of Aspergillipeptide D for normal and drug-resistant HSV-1 viruses and to use HSV-1 latent infectious model researched the influence of Aspergillipeptide D on viral latency.The influence on viral different kinds of action modes of Aspergillipeptide D was detected by plaque reduction assay,qPCR and Western blotting.The antiviral molecular mechanism of Aspergillipeptide D was researched initially by LSCM,IP and MS.Results: Aspergillipeptide D had a low cytotoxicity of Vero cells,with the value of CC50 equalling 208.723±9.717?M.Aspergillipeptide D had significant antiviral activities on both nomal and drug-resistant HSV-1 viruses meanwhile it could promote the expression of viral acute infectious related genes in latency;Aspergillipeptide D wasn't able to inactivate virus and had no effect on viral attachment and penetration,but it had a therapeutic effect post infection of HSV-1 with concentration dependence and time dependence significantly.Aspergillipeptide D inhibited the viral spread meanwhile;Aspergillipeptide D had no difference to viral DNA replication,but it inhibited the expression of viral late genes.Especially,Aspergillipeptide D impacted the expression and location on ER and Golgi apparatus of viral late glycoprotein gB significantly,and inhibited the ineraction of gB and other cellular proteins.Conclusions: Aspergillipeptide D has significant antiviral effect on nomal and drug-resistent HSV-1 and has the potency of promoting reactivation of latent virus.Aspergillipeptide D inhibites the expression and the interaction with cellular proteins of the viral late protein gB therefore it influences viral infection and spread further.gB is the potential antiviral target of Aspergillipeptide D.