Abstract
To inhibit HIV replication and infection, we have designed novel linear single stranded modified antisense nucleic acid oligonucleotides ending with or without chain terminating bases (Which resemble the shape of the comb). They were targeting specifically the HIV-1 clone pNL4-3 strong promoter pre PBS region to stop cDNA synthesis within or before the R region, preventing the viral reverse transcriptase (RT) jumping to the 3' end and continue copying the virus. The main advantages of our comb shaped oligonucleotides are their specificity and extreme protection against resistance by known viral mutations. Promising results were obtained for two 15-mer compounds at one tenth azidothymidine concentration. As a result we claim that when adapted properly, the comb shaped antivirals can be used to target the genomic RNA of a number of serious viruses such as for example Ebola, SARS-CoV-2, Influenza, Dengue, hepatitis C, Chikungunya and Zika as they are all using polymerases to copy their genomic RNA1-8. Their genomic RNA could be destroyed through the human or viral endonucleases instead of the viral RT RNAseH site when their polymerases are stopped at specific sites.
586. Dimerization Inhibition of HIV-1 RNA by 2’-Deoxy-2’-fluoro-beta-D-arabinose Nucleic Acid (2’-FANA) Modified Antisense Oligonucleotides Results in Potential Inhibition of Viral Expression
