In the history of human beings who have suffered with various bacterial and viral infections from old, the discovery of antibiotics and the development of vaccines against viruses have brought about a great development in the medical care of this century. However, many chronic and infectious diseases have still presented a serious social problem.
More particularly, the greatest problem which confronts us today includes prophylaxis of infection with viruses such as human immunodeficiency virus (abbreviated as HIV; Barre-Sinoussi et al., 1983; Gallo et.al., 1984) which causes human adult T-cell leukemia (abbreviated as HALT) and human T-cell lymphotropic virus (abbreviated as HTLV; Yoshida et al., 1984) which causes acquired immunological deficiency syndrome (abbreviated as AIDS) and the treatments of theses diseases.
Some of herb medicines and crude drugs constituting the herb medicines have been hitherto believed as having the antiviral action. In recent years, a number of studies and reports have been made on crude drugs having the antiviral action. The antiviral activity itself has been elucidated on about half of the crude drugs, thus leaving many crude drugs to be unclear with respect to the activity. The mechanism of the antiviral action has now been under detailed study. Some reports have been already made on the antiviral action through an immunological regulation activity system.
On the other hand, there is the possibility of developing antiviral agents along the line of the central dogma of the molecular biology, i.e. the flow of deoxyribose nuleic acid (abbreviated as DNA).fwdarw.messenger ribonucleic acid (abbreviated as mRNA).fwdarw.protein.
Additionally, transcription that takes place in the direction opposite the central dogma, i.e. from RNA to DNA (in contrast to the central dogma's flow of DNA to mRNA) also occurs in nature. This has been backed up with the discovery of a reverse transcriptase (abbreviated as RT) made by Temin and Baltimore in 1970 (Baltimore, 1970; Temin and Mizutani, 1970).
Retroiviruses (reverse transcriptase contains oncovirus) are those having reverse transcriptases as is suggested by the name. Specific attention has been paid to the virus since the retroviruses were recognized in 1980's as causing human adult T-cell leukemia and AIDS, whose spread has been viewed with anxiety.
Since then, extensive studies have been made on retroviruses. At present, detailed information has been reported at a gene level and the life cycles of the viruses are now being made clear (Meek et al., 1990a).
The target in the development of antiviral agents is considered to reside in a method of suppressing the attachment of viruses to cells and suppressing the reverse transcription of viral ribonucleic acid toward deoxyribonucleic acid. Typical compounds reported as having the activity of inhibiting reverse transcription include nucleotides, antibiotics, natural products and the like.
Of these, nucleotide derivatives are greatest in number and have been synthesized for the purpose of the competitive inhibiting action of the reverse transcriptase substrate (Nhtsuya and Broder, 1987)
Azidothymidine, 2',3'-dideoxycytidine and 2',3'-dideoxyinosin are typical of these reverse transcriptase inhibitors and are a few medicines authorized as agents for treating for AIDS.