Moreover, years of discovery of HBV (1963), HPV (1965), HIV (1983), and HCV (1989) are indicated, while the other five viruses were discovered before 1959 ( Table 1). For each virus, a colored line demonstrates the total number of approved drugs. The x axis indicates the period from January 1959 to April 2016, and the y axis shows the total number of approved drugs. (B) Timeline of approval of drugs against 9 human infectious diseases (HIV, HBV, HCV, HSV, HCMV, HPV, RSV, VZV, and influenza virus). Movies and label information for approved drugs are accessible online (see ). A list of drug abbreviations is available in Table 2. Therefore, this zodiac-based figure metaphorically recognizes each antiviral drug as a star in the universe, commemorating the significant contributions of antiviral drug discovery and development over the past 50 years. In this picture, every approved drug could be conceived as a “superstar,” and its contribution to human health is worthy of being remembered and respected. A total of 90 stars thus represent all approved antiviral drugs, and each drug star is positioned according to its approval date ( Table 2). Yellow stars indicate approved drugs that have been discontinued or abandoned for clinical use. In the drug group, each red star within a sign represents an approved drug, placed according to the year of approval. Each sign indicates a drug group whose name is annotated outside the circle. The gray arrow shows the dates of approval of antiviral drugs from January 1959 to April 2016. (A) Approved antiviral drugs visualized in the zodiac. History of antiviral drugs approved between January 1959 and April 2016. Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2′-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2′-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox).
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