Inhibition of infectious Rous sarcoma virus production by rifamycin derivative

Abstract

A new rifamycin derivative, rifazone-82 (R-82), an inhibitor of viral RNA-dependent DNA polymerase, is selectively toxic to transformed chicken cells in culture. R-82 has now been shown to possess antiviral activity as well. The relatively nontoxic properties of R-82 to nontransformed cells have permitted the execution of experiments examining the effect of a rifamycin derivative on virus reproduction. Addition of low concentrations of R-82 (15 mug/ml) to cultures soon after Rous sarcoma virus infection prevents the spread of infection thoroughout the culture. This inhibition is not dependent on concomitant cellular transformation as identical results were obtained with cells infected with a transformation-defective Rous sarcoma virus. Addition of R-82 to cultures in which all the cells are infected does not substantially affect the yield of physical particles as measured by RNA-dependent DNA polymerase activity and by (3H) uridine incorporation into viral RNA. However, the infectivity of the progeny virus, as measured by focus-forming ability, is decrreased 95 to 99% by R-82 treatment.

Cloning and sequence analysis of the putative rifamycin polyketide synthase gene cluster fromAmycolatopsis mediterranei

“…Some rifamycin derivatives have been found to be effective against difficult‐to‐treat M. avium and M. intracellulare infections in patients with AIDS [2], and against pneumococci with decreased susceptibility to penicillin [3]. Rifamycins with lipophilic side chains were found to be active at higher concentrations against RNA tumor viruses [4].…”

Cloning and sequence analysis of the putative rifamycin polyketide synthase gene cluster from Amycolatopsis mediterranei

“…Some rifamycin derivatives have been found to be e¡ective against di¤cult-to-treat M. avium and M. intracellulare infections in patients with AIDS [2], and against pneumococci with decreased susceptibility to penicil-lin [3]. Rifamycins with lipophilic side chains were found to be active at higher concentrations against RNA tumor viruses [4].…”

Antivirals: Past, Present and Future

“…Furthermore, rifampin inhibits poxvirus replication in vitro via a mechanism other than inhibiting DNA-dependent RNA polymerase. In vitro screening for selective inhibition of RNA-dependent DNA polymerase (reverse transcriptase) on a number of derivatives revealed that certain derivatives prevented focus formation by RNA tumour viruses (Szabo et al 1976). Rifamycin derivatives were also found to act against type II DNA topoisomerases.…”