March 1, 1986Open Access
Antirhinovirus activity of purine nucleoside analogs
Key Result
Tubercidin and several analogs potently inhibited rhinovirus replication at concentrations below 1 µg/ml but lacked selectivity, whereas 3-deazaguanine emerged as the most selective inhibitor with a selectivity index of 50.
Structured PICO
P
Population
In vitro study evaluating purine nucleoside analogs against rhinovirus types 1A, 1B, and 9 in human diploid (WI-38) fibroblasts.
I
Intervention
Purine nucleoside analogs (including tubercidin, adenosine analogs, toyocamycin, sangivamycin, and 3-deazaguanine)
O
Outcome
Antirhinovirus activity (inhibition of rhinovirus replication) and cytotoxicitysurrogate
While several purine nucleoside analogs potently inhibit rhinovirus replication, their narrow therapeutic window due to cytotoxicity limits utility, with 3-deazaguanine showing the best selectivity.
Limitations
- Lack of selectivity for most potent compounds, with cytotoxicity occurring at concentrations only 3- to 10-fold higher than the MIC.
- In vitro results may not translate to clinical efficacy, as previously observed with other antirhinovirus compounds.
- The virus yield reduction achieved by 3-deazaguanine was only transient.
Abstract
A wide variety of purine nucleoside (mainly tubercidin and adenosine) analogs, which had previously been shown to inhibit the replication of a broad spectrum of RNA viruses, were evaluated for their antirhinovirus activity in human diploid (WI-38) fibroblasts. Tubercidin, 5-(1-hydroxyethyl)tubercidin, 5-(2-buten-1-yl)tubercidin, toyocamycin, and sangivamycin emerged as the most potent inhibitors. These compounds inhibited the replication of rhinovirus types 1A, 1B, and 9 at an MIC well below 1 microgram/ml. However, these compounds proved cytotoxic for the uninfected host cells at concentrations which were only slightly higher (3- to 10-fold, on the average) than those required for inhibition of rhinovirus replication. The most selective inhibitor of rhinovirus replication was 3-deazaguanine, with a selectivity index of 50. None of the carbocyclic and acyclic analogs of adenosine tested exhibited a potent or selective antirhinovirus activity.