Study On The Effects Of Modified Amantadine Against Avian Influenza Virus

Influenza A virus strains are classified as low pathogenic (LPAI) or highly pathogenic (HPAI) on the basis of specific molecular genetic and pathogenesis criteria that require specific testing. HPAI viruses can cause severe illness and high mortality in poultry. Until now, there are no effective methods to control HPAI infection. Nowadays, the drugs used to treat HPAI infection in clinical includes amantadine (AM), an M2 inhibitor which blocks the ion channel formed by the M2 protein, Oseltamivir, a neuramidinase inhibitors and adamantane triethylamine. However, these drugs have some side effects and resistance. Therefore, it is urgent to develop new drugs with higher antiviral effect, lower toxicity and independent intellectual property rightsIn this paper, 3 test compounds, NAM, LAM and SAM were synthesized by self-assembly method. The parent compound of test compounds is amantadine, the ligand is micromolecule compounds.In the experiment, toxicity and antiviral activity and immunoregulatory activity were evaluated in vitro and in vivo, respectively. The toxicity of NAM, LAM and SAM in vitro: the CPE and MTT assay were used to detect the toxicity of the test compounds in vitro. The result showed the TC50 and TC0 of the test compounds were higher than that of AMA, indicating the test compounds have lower toxicity.The toxicity of NAM in vivo: the acute toxicity of NAM in vivo was detected. The result showed the LD50 of NAM was 800mg·kg-1 , indicating the NAM was compound with low toxicity.The antiviral activity of NAM, LAM and SAM in vitro: the cell culture method was used to detect the antiviral activity of test compounds in vitro. The result showed the TI was higher than that of AMA, indicating the NAM have better antiviral activity and the safety range is wider than that of AMA.The anti-H5N1 activity of NAM in vivo: the mice infected with H5N1 were used to detect the anti-H5N1 activity in vivo. The result showed compared with the control group, the mortality of infected mice was decreased significantly, the survival rate of infected was increased and the average living days was lengthened. The body weight of mice treated with the test compound kept stable. The humid weight of lung of infected mice was decreased significantly. Pathological changes in lung of infected mice were lessened. Proliferation of the H5N1 in lung of infected mice was inhibited. Pneumonic symptom of the infected mice inhibited obviously.In words, NAM has some characterizations: the toxicity is low, the antiviral activity is high.Conclusion: the modified amantadine has lower toxicity and better antiviral activity, the antiviral activity is higher than that of AMA.