Противовирусные нуклеотиды

Antiviral nucleotides are nucleotide analogs that repress the viral reproduction by interfering with several key mechanisms of viral nucleic acid replication. They compete with natural dNTP/NTP substrates for the incorporation into the nascent viral nucleic acid thereby leading to chain termination or mutagenesis (Tab. 1).

Nucleotide	Analog of...	Incorporation by viral...	Mechanism of inhibition
Lamivudine triphosphate	...Cytidine triphosphate	...Reverse Transcriptase[1]	Chain termination of viral cDNA synthesis
Stavudine triphosphate	...Thymidine triphosphate	...Reverse Transcriptase[2]	Chain termination of viral cDNA synthesis
Zidoduvine triphosphate	...Thymidine triphosphate	...Reverse Transcriptase[3]	Chain termination of viral cDNA synthesis
Aciclovir triphosphate	...Guanosine triphosphate	...DNA polymerase[4]	Chain termination of viral DNA synthesis[4]
Vidarabine triphosphate	...Adenosine triphosphate	...DNA polymerase[5]	unknown
Ribavirin triphosphate	...Guanosine triphosphate	...RNA polymerase[6]	Mutagenesis of viral genome replication[6]

In vivo or cell culture experiments can be performed using the non-phosphorylated nucleoside variant of an antiviral nucleotide that is intracellularly metabolized by multiple viral and/or host kinases to its active, the antiviral effect exerting (tri)phosphorylated forms (NMP → NDP → NTP)^[7,8].

Alternatively, a number of mono- and triphosphorylated forms of antiviral nucleotides are available for functional in vitro experiments (Tab. 2).

Please refer to the corresponding data sheet for detailed application data.

Nucleoside	Nucleotide Monophosphate (NMP)	Nucleotide Triphosphate (NTP)
3TC (Lamivudine)	3TCMP	3TCTP
d4T (Stavudine)	d4TMP	d4TTP
AzT (Zidovudine)	AzTMP	AzTTP
ara-A (Vidarabine)	ara-AMP	ara-ATP
Aciclovir	Aciclovir monophosphate	Aciclovir triphosphate
Ribavirin	Ribavirin monophosphate	Ribavirin triphosphate

Фармацевтические исследования