Antiviral activity and mechanism of action of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860)

A nitrobenzene derivative, MDL-860, was found to inhibit plaque formation, cytopathic effect, or both in 11 of 12 picornaviruses at concentrations which did not affect cell growth. The compound did not directly inactivate the virus. MDL-860 inhibited actinomycin D-resistant [3H]uridine uptake in cells infected with coxsackievirus A21 or rhinovirus 1-A, whereas incorporation into uninfected cells was not inhibited. With three picornaviruses (echovirus type 12, poliovirus type 2, and rhinovirus type 1-A) made photosensitive with neutral red, MDL-860 did not appear to cause a significant reduction in their loss of photosensitivity (uncoating) during the first 3 h of infection. MDL-860 appears to inhibit some early event in virus replication, after uncoating, which is required for synthesis of a majority of viral RNA.