INHIBITION OF MOUSE HEPATITIS-VIRUS MULTIPLICATION BY PHOSPHOROTHIOATE ANALOGS OF OLIGODEOXYNUCLEOTIDES COMPLEMENTARY TO THE LEADER RNA

Phosphorothioate oligodeoxynucleotides (PS-oligo) complementary to a l eader RNA of mouse hepatitis virus (MHV) were more effective inhibitor s of MHV multiplication than natural oligodeoxynucleotides (PO-oligo). Sequence-dependent inhibition of viral multiplication was shown at lo w concentrations (0.001-0.1 mu M) of antisense PS-oligo. Phosphorothio ate oligodeoxycytidine, PS-(dC)(20) and PS-oligo, which has no signifi cant homology to the MHV sequence, showed inhibitory effects on MHV mu ltiplication at concentrations higher than 0.5 mu M. These results sho wed that PS-oligo was more potent than PO-oligo in inhibition of MHV m ultiplication and that PS-oligo may inhibit MHV multiplication by two different mechanisms, that is, in sequence-dependent and -independent manners.