Increased stability and antiviral activity of 2′‐O‐phosphoglyceryl derivatives of (2′‐5′)oligo(adenylate)

Abstract

Metabolically stable analogs of (2''-5'')oligo(A), (2''-5'')(A)n, might constitute a new class of antiviral agents as they mimic some of the effects of interferons. 2''-O-phosphoglyceryl derivatives of (2''-5'')(A)n oligomers, (2''-5'')(A)n-PGro were synthesized by chemical modification of their terminal ribose residue. Such analogs are resistant to degradation by phosphodiesterases but remain sensitive to phosphatase activity, at least in cell-free extracts. In line with its increased stability, (2''-5'')(A)n-PGro has a powerful antiviral activity against an RNA virus when microinjected with micropipettes into the cytoplasm of intact cells. This antiviral activity remains transient however, possibly as a consequence of degradation in intact cells. Since (2''-5'')(A)n and its derivatives do not easily cross cell membranes, their possible use in antiviral chemotherapy is tightly linked with the development of vectors suitable for their administration in vivo.