Download - Replicative cycle of HIV-1 and Therapy
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Replicative cycle of HIV-1 and Therapy
Entry
Reverse Transcription
Integration
Maturation
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Polymerase and RNase H active sites of HIV-1 RT
17-18 bp
p51
p66
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p66
p51
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DNAn+1DNAn
dNTP PPi
DNAn+2 ...
dNTP PPi
DNA synthesis
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N
C
H
3
N
O
N
N
Cl
N
O
O
F
3
C
H
Nevirapine
Efavirenz
Structures of NON-nucleoside analogue RT inhibitors (NNRTIs)
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HIV-1 RT Bound to a Non-Nucleoside RT Inhibitor(NNRTI)
Active site
Nevirapine
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HIV-1 RT Bound to a NNRTI + Surrounding NNRTI-associated Drug Resistance Mutations
Active site
Nevirapine
Drug resistance mutations
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N
H
O
C
H
3
O
N
O
Ho
O
H
Thymidine
N
H
O
C
H
3
O
N
O
Ho
N
3
N
H
O
C
H
3
O
N
O
Ho
O
N
N
H
2
N
O
Ho
O
H
Cytidine
O
N
N
H
2
N
O
S
Ho
AZT d4T
3TC
Structures of nucleoside analogue RT inhibitors (NRTIs)
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HIV-1 RT: Active Site and NucleosideAnalog Drug Resistance Mutations
Active site
Incoming nucleotide
Drug resistance mutations
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HIV-1 Protease Bound to an Inhibitor
Substrate Cleft:
Active site:
Indinavir
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HIV-1 Protease Bound to Inhibitor + Drug Resistance Mutations
Substrate Cleft:
Active site:
Indinavir
“Major” mutations
“Minor” mutations