Based On The The Sah Enzymatic Mechanism Of Virus Inhibitor Design

Virus is so far the smallest pathogenic microorganism within our knowledge scope, mainly constituted by proteins and nucleic acids. It has a very simple structure, mostly lack of enzyme system, can only depends on host cells to replicate its nucleic acids and proteins which are assembled as virus particle for proliferation. Virus infection causes many kinds of diseases doing great harm to human health and life. In recent years new types of anti-virus drugs appear continuously. However, incidence of virus infection is not decreasing, especially when AIDS and its pathogenic virus appear in the 80s of 20th century, which urgently required research into and development of anti-virus drugs. As clinic use of anti-virus drugs expands, doctors and patients have raised higher and higher requirements. Therefore investigation into anti-virus drugs has become one of the hottest issues of international researches.Biological transmethylation is a critical step in virus replication process, in which S-adenosyl methionine, SAM is methyl donor. Meanwhile, the product of this reaction S-adenosylhomocysteine (AdoHcy) inhibits reaction in reverse. In reaction with S-adenosylhomocysteine hydrolase (SAHH)。S-adenosylhomocysteine is hydrolyzed to adenosine and L-homocysteineTherefore once we inhibit the activity of S-adenosylhomocysteine hydrolase, virus life cycle will be blocked. Our investigation focuses on the substances that are able to inhibit SAH.Accordingly, in order to find more effective anti-virus active compounds with low toxicity, I have performed work as follows:1. Searching for new anti-virus drugs using modern cheminformatic methods and Traditional Chinese Medicine Database. Using inhibitor of SAHH—Adc as the template, we conducted similarity search in TCMD and find 17 compounds with high similarity. After that these 17 compounds and the natural inhibitor were virtually docked into the hydrolase by Autodock3.0.1 and 6 ligands were screened out with docking results. Fig. 1. 6 ligands screened out with docking results.2. We made comparisons among the best results, discussed the mechanism of inhibition reaction and modified the best resolutions with the intention to obtain wide-spectrum anti-vires drugs.Fig. 2. Structures of proposed inhibitor models, in whichⅩrepresents CH or CH-CH3.