Inhibition of Cytomegalovirus Replication by Smooth-Muscle Relaxing Agents

Abstract

The effect of the smooth-muscle relaxing agents, papaverine, sodium nitroprusside, and verapamil, on the replication of human cytomegalovirus (CMV) was investigated. At a concentration of 100 microM, infectious yields of CMV were reduced by 1.23 to 5.72 log10 by these drugs (papaverine, 5.72 log10; nitroprusside, 1.85 log10; verapamil, 1.23 log10). The ED50 for papaverine was found to be somewhat less than 1 microM, a concentration which appears to be within the range achieved clinically. Papaverine did not irreversibly modify treated cells to a virus-resistant state since treatment of cells with papaverine from 24 hr before until immediately prior to CMV infection did not significantly reduce CMV yields. Replication of CMV was most sensitive to inhibition when papaverine was added at or before 6 hr after CMV infection. Addition of papaverine at later times resulted in a substantial reduction of the inhibitory effect on virus yields, suggesting that the phase of CMV replication sensitive to papaverine inhibition occurred early in the replication cycle. These results, particularly in light of the potency of papaverine, indicate that some smooth-muscle relaxing agents have significant antiviral activity toward the replication of CMV.