Three new powerful oseltamivir derivatives for inhibiting the neuraminidase of influenza virus.
Owing to its unique function in assisting the release of newly formed virus particles from the surface of an infected cell, neuraminidase, an antigenic glycoprotein enzyme, is a main target for drug design against influenza viruses. The group-1 neuraminidase of influenza virus possesses a 150-cavity, which is adjacent to the active pocket, and which renders conformational change from the 'open' form to the 'closed' form when the enzyme is binding with a ligand. Using AutoGrow evolutionary algorithm, one very unique fragment is screened out from the fragment databases by exploiting additional interactions with the 150-cavity. Subsequently, three derivatives were constructed by linking the unique fragment to oseltamivir at its three different sites. The three derivatives thus formed show much stronger inhibition power than oseltamivir, and hence may become excellent candidates for developing new and more powerful drugs for treating influenza. Or at the very least, the findings may stimulate new strategy or provide useful insights for working on the target vitally important to the health of human beings.
Wang
Shu-Qing
SQ
School of Pharmaceutical Sciences, Tianjin Medical University, Tianjin, China. sqwang@gordonlifescience.org
Cheng
Xian-Chao
XC
Dong
Wei-Li
WL
Wang
Run-Ling
RL
Chou
Kuo-Chen
KC
D000998:Antiviral Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015707:HN Protein / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D009975:Orthomyxoviridae / Q000187:drug effects / Q000201:enzymology*; D053139:Oseltamivir / Q000031:analogs & derivatives*; D011487:Protein Conformation
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D015707:HN Protein; D053139:Oseltamivir