Timothy H. Cronin

Chapter 12. Antiviral Agents

Publisher Summary This chapter describes the development and clinical studies of antiviral agents. The role of RNA directed DNA-polymerase with regard to oncogenic viruses has been examined and a search for inhibitors of this enzyme as potential antiviral agents has focused on the ansamacrolides. Isoprinosine is claimed to have a range of antiviral activity in experimental laboratory infections and uncontrolled human trials claiming efficacy have been reported. Human interferon has a limited but measurable activity against a number of strains of adenovirus. The absence of interferon in serial serum specimens collected prior to and during the incubation and acute phase of transfusion associated hepatitis may in part be related to the chronicity of the disease. Innoculation of mice with Friend virus results in a progressive increase in spleen size, followed by eventual rupture and death. Administration of double-stranded RNA prior to or in the early stages of infection increases the severity of the disease, whereas treatment with the RNA beginning 5 days after infection causes a marked reduction in spleen size and a more normal histological appearance of the spleen. Chlorite oxidized oxyamylose protects mice against foot and mouth disease virus but did not protect swine against the natural infection.

Chapter 13. Antiviral Agents

Publisher Summary This chapter discusses studies on antiviral agents with an emphasis on interferon. The role played by interferon in the course of natural varicella infection was studied in human patients with and without impairment of host–defense mechanisms. With normal defense mechanisms, interferon titres present in cutaneous vesicles were initially high and appeared to prevent virus dissemination and allow rapid recovery. On the other hand, in patients with Hodgkins disease, lymphomas, and leukemias, where there is an impairment of host–defense mechanisms, low titres of cutaneous interferon were initially present, and viral dissemination was rapid and in some cases led to death. In those cases, which were resolved favorably, the remission followed the late appearance of high interferon titres. In animal experiments, it was found that macrophages stimulated to produce interferon by a nonreplicating virus could be transferred to mice already infected with encephalomyocarditis (EMC) or Semliki Forest (SFV) virus and exhibiting clinical symptoms. Some early studies of poly IC in man have shown that a low titre of interferon (1:16) is achieved after intravenous administration. No effect on prolongation of life or alleviation of the disease conditions was seen in terminal cancer patients after intravenous administration of poly IC, but the only side effect noted was mild fever.