Design of nucleoside, oligonucleotide and polynucleotide analogues as antiviral agents.
Several approaches can be envisaged in the design of nucleoside and oligo- or polynucleotide analogues with selective antiviral activity: (i) deoxythymidine (dThd) or deoxycytidine (dCyd) analogues which are specifically recognized as substrate by the virus-induced dThd-dCyd kinase; (ii) adenosine analogues which impair transmethylation reactions (or polyamine biosynthesis), by virtue of an inhibition of S-adenosylhomocysteine hydrolase; (iii) (2'-5')-oligonucleotide analogues derived from pppA(2'p5'A)2, an important intermediate in the antiviral action of interferon; (iv) oligo(deoxy)nucleotides that are complementary to a well-defined nucleotide sequence of the viral genome; (v) single-stranded homopolynucleotides that act as antitemplates for virus-associated RNA or DNA polymerases; and (vi) double-stranded homopolynucleotides that may be pursued for their interferon-inducing potentials.
D000241:Adenosine / Q000031:analogs & derivatives; D000998:Antiviral Agents; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D011119:Polynucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives; D014780:Viruses / Q000187:drug effects
D000998:Antiviral Agents; D009705:Nucleosides; D009841:Oligonucleotides; D011119:Polynucleotides; D003841:Deoxycytidine; D012194:RNA-Directed DNA Polymerase; D012321:DNA-Directed RNA Polymerases; D004259:DNA-Directed DNA Polymerase; D000241:Adenosine; D013936:Thymidine