Formation of vaccinia virus DNA-protein complex in the presence of isatin beta thiosemicarbazone (IBT).

The association of newly synthesized vaccinia virus DNA with proteins in infected HeLa cells was followed. A shift from a high density to a low density complex occurred between 3 and 6 h after infection. This process was not affected by isatin beta thiosemicarbazone (IBT), an inhibitor of pox virus growth. At 22 h after infection in the absence of IBT, mature virions of high density were observed; however, in the presence of the drug, high density DNA-protein complexes, which lack the two main virus core polypeptides, were formed.

Inhibition of vaccinia virus growth by the nucleoside analogue 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ribavirin).

Virazole or Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits the growth of vaccinia virus at a concentration ode to a certain extent in the presence of Virazole, the DNA fails to acquire resistance to deoxyribonuclease and virus particles are not formed. Reversibility of the antiviral effect occurs when the drug is washed out from the infected cultures or when guanosine at an equimolar concentration is added.

The effect of tilorone hydrochloride on the growth of several animal viruses in tissue cultures.

Tilorone hydrochloride, at a concentration of 10 mug/ml inhibits the growth of herpes simplex virus type 1 in BS-C-1 cells. The growth of vaccinia virus in BS-C-1 cells is partially inhibited; however, six viruses containing RNA, including four members of the togavirus group grown in chick fibroblasts, are not affected by the drug. The inhibition of the growth of herpes virus by tilorone hydrochloride is greater when the multiplicity of infection is lower than 1 p.f.u/cell and when the drug is added early in the course of infection.

Inhibition of herpesvirus deoxyribonucleic acid and protein synthesis by tilorone hydrochloride.

Tilorone hydrochloride at a concentration of 10 mug/ml very efficiently inhibited herpes simplex virus growth in BSC1 cells when the virus is infected at a low multiplicity of infection. The adsorption of the virus was not affected by the drug, and the penetration of the deoxyribonucleic acid of the input virus into the cytoplasm and nuclei proceeded normally when tilorone hydrochloride was present. However, newly synthesized viral deoxyribonucleic acid was not detectable under these conditions, there was a remarkable decrease in the rate of viral polypeptide synthesis, and virus particles were not formed. The inhibition of herpesvirus growth by tilorone hydrochloride was absolutely dependent on the presence of the drug in the cultures. Pretreatment of the cells with the drug did not result in resistance to herpesvirus infection after the removal of the drug.

Inhibition of the growth of hemadsorption 2 virus by three acyl derivatives of amino acids.

Three acyl derivatives of amino acids, dicarbobenzoxy-l-lysine sodium, carbobenzoxy-l-aspartic acid-beta-benzyl ester potassium, and N-3-phenylpropionyl-S-benzyl-l-cysteine potassium inhibit the growth of parainfluenza 1 (hemadsorption 2) virus. The growth of simian virus 40, vaccinia, poliomyelitis type 1, Semliki Forest, Eastern equine encephalitis, and Western equine encephalitis viruses was not affected by these compounds. Four other acyl derivatives of amino acids did not inhibit the growth of any of the viruses tested.

Isolation and characterization of a gamma-thiochromanone-4-thiosemicarbazone-resistant mutant of vaccinia virus.

gamma-Thiochromanone-4-thiosemicarbazone (TCT) inhibits the growth of vaccinia virus in BSCl cells by interfering with viral maturation. A mutant of the virus (TCT(R)) which is resistant to this drug was isolated. This mutant also exhibits resistance to another thiosemicarbazone related compound, isatin beta-thiosemicarbazone (IBT). There is a good correlation between the cross-resistance of the two mutants IBT(R) and TCT(R) to TCT and IBT, respectively, and the similar antipoxvirus activity of these two thiosemicarbazone-related compounds.

Synthesis of vaccinia virus polypeptides in the presence of hydroxyurea.

Hydroxyurea (5 x 10(-3) M) inhibits the development of vaccinia virus in HeLa cells early after infection and prevents the synthesis of viral deoxyribonucleic acid. In the presence of hydroxyurea, late viral polypeptides are not formed, as observed by electrophoresis on polyacrylamide gels.

Synthesis of vaccinia virus polypeptides in the presence of isatin-beta-thiosemicarbazone.

Isatin-beta-thiosemicarbazone (IBT) at a concentration of 14 muM inhibited the multiplication of vaccinia virus in HeLa cells. For the first 3 h after infection, viral deoxyribonucleic acid (DNA) was synthesized in the presence of IBT at the same rate as in the control culture; the replication rate declined at a later stage. The DNA failed to be coated with proteins and to become resistant to deoxyribonuclease unless IBT was removed. "Early" and "late" viral polypeptides were formed in the presence of IBT, as revealed by polyacrylamide gel electrophoresis. The formation from precursor of a core polypeptide, a reaction blocked by rifampin, was not affected by IBT. Therefore, it is suggested that a maturation step later than the one blocked by rifampin is involved in the inhibition of vaccinia virus by IBT.