Abstract

Microvirin (MVN) is a carbohydrate-binding protein which shows high specificity for high-mannose type N-glycan structures. In the present study, we tried to identify whether MVN could bind to high-mannose containing hepatitis C virus (HCV) envelope glycoproteins, which are heavily decorated high-mannose glycans. In addition, recombinantly expressed MVN oligomers in di-, tri- and tetrameric form were evaluated for their viral inhibition. MVN oligomers bound more efficiently to HCV virions, and displayed in comparison with the MVN monomer a higher neutralization potency against HCV infection. The antiviral effect was furthermore affected by the peptide linker sequence connecting the MVN monomers. The results indicate that MVN oligomers such as trimers and tetramers may be used as future neutralization agents against HCV infections.

Highlights

  • Hepatitis C virus (HCV) is a major health concern with estimated 130–200 million people infected worldwide [1]

  • We found that all MVN oligomers can completely inhibit cell culture-derived HCV (HCVcc) at a concentration of 1 μM; a similar effect was observed for the MVN monomer, which displayed approximately 94% inhibition (Figure 4A)

  • We found that all MVN oligomers showed improved neutralization of cultured hepatitis C virions and of HCV in human serum samples compared with the MVN monomer

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Summary

Introduction

Hepatitis C virus (HCV) is a major health concern with estimated 130–200 million people infected worldwide [1]. Treatments involving drugs such as telaprevir and boceprevir, which directly inhibit viral HCV NS3/4A protease [9,10], have been considered a breakthrough therapy for the specific treatment of HCV genotype 1b infection by the FDA in 2011 [11]. These protease inhibitors are less effective against genotype 3 in all seven HCV genotypes, and drug resistance may develop due to rapid mutational adaption [12]. The discovery of novel compounds with antiviral mechanisms distinct from those of known anti-HCV agents, and which can be applied alone or in a combination with existing drugs, is highly desirable and much needed

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