Biomedical Engineering Reference
In-Depth Information
His 274
Tyr 252
Glu 276
Thr 252
250-N
FIGURE 24.17 Locations of oseltamivir-resistance mutations (H274Y) showing that the tyrosine at position
252 is involved in a network of hydrogen bonds in group-1 (H5N1 and H1N1) neuraminidases. (After Russell,
R.J. et al., Nature , 443, 45, 2006.)
Activity spectrum : Inl uenza (A and B) virus.
Mechanism of action : Zanamivir and oseltamivir (see below) are N -acetylneuraminic (sialic acid)
analogues, which are targeted at the inl uenza viral neuraminidase (sialidase) (Figure 24.17). The
viral neuraminidase is responsible for the cleavage of N -acetylneuraminic acid present in the inl u-
enza virus receptor so that progeny virus particles can be released from the infected cells. The
neuraminidase inhibitors zanamivir and oseltamivir keep the virus trapped onto the surface of the
cells so that they cannot be released and hence cannot infect other cells.
Principal indication(s) : Inl uenza A and B viral infections (therapy and prevention).
Administered : By (oral) inhalation, at a dosage of 20 mg/day (two times 5 mg, every 12 h) for 5 days.
Treatment to be started as early as possible, and certainly within 48 h, after onset of the symptoms.
24.5.4 O SELTAMIVIR
Structure (Figure 24.16): Ethyl ester of (3 R ,4 R ,5 S )-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-
cyclohexane-1-carboxylic acid, GS 4104, Ro 64-0796, Tamil u ® .
Activity spectrum : Inl uenza (A and B) virus.
Mechanism of action : As for zanamivir.
Principal indication(s) : As for zanamivir.
Administered : Orally at 150 mg/day (two times a 75 mg capsule, every 12 h) for 5 days. Treatment
should be started as early as possible, and certainly within 48 h, after onset of the symptoms.
24.5.5 R IBAVIRIN
Structure (Figure 24.16): 1-
β
-d-Ribofuranosyl-1 H -1,2,4-triazole-3-carboxamide, Virazole ® , Virazid ® ,
Viramid ® .
Activity spectrum : Various DNA and RNA viruses, in particular orthomyxoviruses (inl uenza A
and B), paramyxoviruses (measles, RSV) and arenaviruses (Lassa, Junin, etc.).
Mechanism of action : The principal target for ribavirin (in its 5
-monophosphate form) is IMP dehy-
drogenase, that converts IMP to XMP, a key step in the de novo biosynthesis of GTP and dGTP. In its
5
-triphosphate form, ribavirin can also interfere with the viral RNA polymerase and in the formation
of 5
-capped oligonucleotide primer that is required for transcription of the inl uenza RNA genome.
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