Anti-influenza A Virus Effects Of Cyanovirin-n (CVN) And Its Derivatives In Vitro And In Vivo

Influenza has serious impacted on human life in worldwide. It causes tens and thousands ofdeaths each year and gradually attracts a global public health concerns. Due to the minority ofspecific anti-influenza drugs in clinical usage as well as the emergency of resistant variant, it ishigh urgent to research and develop more novel drugs for prevention and control flu.Cyanovirin-N （CVN）, firstly found in1997, exhibited phenomenon biological activity ininhibiting a variety of enveloped viruses, include influenza A/B virus. However, due to itscyanobacterial origin, CVN demonstrated unavoidably typical drawbacks in pharmaceuticalapplications, such as a short plasma half-life, proteolysis and immunogenicity. Our groupprepared CVN and its derivatives LCVN and PEG_20k-LCVN which were breakthrough solubleexpression in E. coli. Thus, it is critical to evaluate CVN and its derivatives bioactivities, notonly as a feedback on the preliminary work, but also as a guidance of the next drugabledevelopment.In these work, we evaluated the potential of CVN and its derivatives in anti-influenza virusat multiple levels. By ELISA and hemagglutination inhibition test, we identified that CVN andits derivatives could interact with glycoprotein HA which from different strains in aconcentration-dependent manner.At the celluar level, the cytotoxicity of CVN, LCVN and PEG_20k-LCVN to MDCK cell hadsharply decreased determined by MTT. All three agents can inhibit different influenza strainsproliferation. Besides, PEG_20k-LCVN showed the highest antiviral selectivity index （SI）. Addingagents at different time revealed that CVN and derivatives could directly inactivate IAV, preventviral attach to host cell. CVNs performed their antiviral role mostly at the early infection stage.At the animal experiment level, chicken embryo and mice assays showed that the CVN andits derivatives could inhibit viral activity in vivo, prolong the time of mice death, enhance theprotection mice from death, reduce lung tissue lesions, decrease lung index and pulmonary virustiters. Therefore, CVN derivatives have potential antiviral activity in vitro and in vivo. They canbe used for further development of antiviral drugs.