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Oseltamivir
Neuraminidase inhibitor
2014.05.02
Lee, sang-hwi
Chemical structures of antiviral drugs inhibiting the
neuraminidase of influenza A virus
capsid
1)
2)
3)
4)
5)
6)
7)
8)
Attachment
Fusion
Reverse transcription
Integration
Transcription
Translation
Viral assembly
Budding and maturation of HIV virion
• Retrovirus는 lipid envelope에 의해 둘러싸여 있는
protein capsid안에 packaged된 RNA genome을 가지
는 infectious particle이다.
• lipid envelope은 infection 과정 초기에 host cell의
membrane receptor와 결합할 수 있는 receptor
binding protein을 포함하는 polypeptide chain을 가진
다.
• Retrovirus는 유전물질로서 DNA 대신 RNA와 DNA를
만드는 reverse transcriptase을 가지고 있다.
• Retrovirus가 cell에 감염되면, cytoplasm으로 reverse
transcriptase와 RNA를 주입된다.
• 그 후, chromosomal DNA를 생성하고 host DNA에
삽입되어 복제를 시작한다
JAMA. 2002;287(13):1635-1637
http://www.youtube.com/watch?v=kSLRmj0APZw&feature=youtu.be
Binding of sialic acid–mimic drugs zanamivir and oseltamivir to neuraminidase
zanamivir (yellow)
oseltamivir (green)
sialic acid (gray)
Nature Structural & Molecular Biology 2010, 17, 530
The action of neuraminidase in the continued replication of virions in the
setting of influenza infection.
CMAJ 2011, 183,E420-E422
Neuraminidase
 Glycoside hydrolase enzymes
 Cleave the glycosidic linkages of neuraminic acids.
 Drug target for the prevention of the spread of influenza infection.
 The viral neuraminidases are frequently used as an antigenic determinants
found on the surface of the Influenza virus.
 Neuraminidases, also called sialidases, catalyze the hydrolysis of terminal
sialic acid residues from the newly formed virions and from the host cell
receptors.
 Sialidase activities include assistance in the mobility of virus particles
through the respiratory tract mucus and in the elution of virion progeny from
the infected cell.
Binding mode of action
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