The Key Techniques Establishment Of Anti-H1N1Pharmacodynamic Research And Their Applications In The Research On New Drugs

The widespread of influenza viruses，particularly of influenza A virus subtypeH1N1，pose serious risks to human health and can be developed to life-threateningdiseases. However，although initially beneficial，most anti-influenza virus drugs inclinic，including M2protein ion channel inhibitors and neuraminidase inhibitors，are challenged by high side effects and emergence of drug-resistant viruses. Thus，it represents a urgent demand to develop new potent and specific drugs. In thisstudy，a new compound KA-22was identified with a significant anti-H1N1activitywith IC50of344.4μM in ELISA tests. It also exhibited high binding affinity to NPand HA protein of H1N1in Biacore Tests. Furthermore，to explore the possibilityof minimizing potential side effects and maximizing potency， KA-22wascombined with oseltamivir and the anti-H1N1activity was measured by ELISA，synergy was calculated using Macsynergy. It was shown that both KA-22and LianHua Qing Wen were synergistic with oseltamivir.Furthermore， computer simulating docking was employed to forecast andidentify the targets of KA-30，another nano form of KA-22due to a differentnanorize process. KA-30shares the same functional part with KA-22but possess theadded advantage of identified structure of nanomaterial part. So it is credible to dosimulating study of KA-30instead of KA-22. The data shown that KA-30present ahigh affinity to HA，NA and NP protein of H1N1virus and it’s anti-H1N1activitywas confirmed in previous study. In addition，simulating and predicting ADEMTmodule of Discovery Studio were used to forecast the ADEMT characters of KA-30to provide pharmacodynamics information for the following clinical research.