Screening Of Chemical Synthetic Drugs Against To Avian-like H1N1 Swine Influenza Virus Selection And Evaluation Of Antiviral Activity

The purpose of this study is to screen new chemical synthetic drugs with anti-influenza effect,and to select the chemical synthetic drugs with good inhibitory effect for further study,so as to lay some experimental foundation for the development of chemical synthetic anti-influenza drugs.Using MTT,Real-time PCR,and CPE observation,a rapid,reliable and multi-link cell-level drug screening method was established.The toxicity of 36 newly synthesized drugs and their antiviral effects on avian-like H1N1 swine influenza virus were evaluated by the above methods（Direct inactivation;Inhibition of adsorption;endocytosis,dehulling,Inhibition of virus endocytosis,shelling,nucleic acid and protein replication）,Finally,S-tryptophan benzamide derivatives with good anti-influenza effect were obtained at the cellular level,and the drug number g-28 was obtained.The results showed that the EC₅₀of g-28against avian-like H1N1 swine influenza was 55.566μg/ml,TC₅₀was337.593μg/ml,TI was 6.073.The results showed that g-28 had a good inhibitory effect on influenza virus at the cellular level and could effectively protect MDCK cells from being killed by influenza virus.The acute toxicity of g-28 was determined in BALB/c mice.The results showed that the LD₅₀of g-28 in BALB/c mice was 1999.914 mg/kg.The efficacy test of BALB/c mice was carried out by gavage with g-28.The results showed that g-28 could reduce the mortality of mice after infection,reduce the virus titer of influenza virus in lung tissue,and reduce the titer of turbinate and spleen virus.Pathological sections showed that g-28 could reduce the grade of necrosis and infiltration of lung tissue.This study proved that g-28 has good anti-avian H1N1 swine influenza virus activity in vitro and in vivo.