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cdz00 | ACSJCA | JCA10.0.1465/W Unicode | research.3f (R3.6.i10:44431 | 2.0 alpha 39) 2015/07/15 14:30:00 | PROD-JCA1 | rq_3838209 | 8/06/2015 08:55:23 | 51 | JCA-DEFAULT Review pubs.acs.org/CR 1 Role of Marine Natural Products in the Genesis of Antiviral Agents †,# ‡ ,†,# 2 Vedanjali Gogineni, Raymond F. Schinazi, and Mark T. Hamann* † 3 Department of Pharmacognosy, Pharmacology, Chemistry & Biochemistry, University of Mississippi, School of Pharmacy, 4 University, Mississippi 38677, United States ‡ 5 Center for AIDS Research, Department of Pediatrics, Emory University/Veterans Affairs Medical Center, 1760 Haygood Drive NE, 67 Atlanta, Georgia 30322, United States 8 *S Supporting Information 18.4. Lectins X 51 18.5. Bioactive Peptides X 52 18.6. Miscellaneous Antivirals Possessing Anti- 53 HIV Activity X 54 19. Antivirals from Porifera Y 55 9 CONTENTS 19.1. Sesquiterpene Hydroquinones Y 56 19.2. Cyclic Depsipeptides Y 57 11 1. Introduction B 19.3. Alkaloids Z 58 12 2. Human Immunodeficiency Virus Demographics B 19.4. Diterpenes AC 59 13 2.1. Nomenclature of HIV/AIDS B 19.5. Sulfated Sterols AC 60 14 2.2. Emergence of Drugs From Marine Sources B 19.6. Miscellaneous Antivirals Possessing Anti- 61 15 2.3. History of AIDS/HIV C HIV Activity AC 62 16 2.4. Description of the Virus G 20. Marine Drugs for the Treatment of Other Viral 63 17 2.5. Virus Replication Cycle G Diseases AC 64 18 2.6. HIV−HCV Coinfection H 20.1. Hepatitis B AC 65 19 3. Pneumonia J 20.2. HCV AE 66 20 3.1. Past Pandemics K 20.3. HPV AE 67 21 3.2. Transmission and Pathogenesis K 20.4. Influenza Virus AE 68 22 3.3. Treatment K 20.5. Respiratory Syncytial Virus AG 69 23 4. Hepatitis B K 20.6. Dengue AG 70 24 4.1. Description of the Virus K 20.7. Herpes Simplex Virus (HSV) AG 71 25 4.2. HBV Viral Replication L 21. In the Pipeline: HIV and HCV Drugs under 72 26 4.3. Treatment L Development AH 73 27 5. Human Papilloma Virus M 21.1. HIV AH 74 28 6. Respiratory Syncytial Virus N 21.2. HCV AI 75 29 6.1. Treatment N 21.3. Pneumonia AI 76 30 7. Hepatitis E N 21.4. HBV AI 77 31 8. Dengue N 21.5. HPV AI 78 32 8.1. Pandemics of Dengue N 21.6. Norovirus AJ 79 33 8.2. Dengue Virus O 21.7. Influenza AJ 80 34 8.3. Transmission, Characteristics, and Treatment O 21.8. RSV AJ 81 35 9. Severe Acute Respiratory Syndrome O 21.9. Shingles AJ 82 36 10. Norovirus O 22. Conclusion AJ 83 37 10.1. Transmission and Treatment O Associated Content AK 84 38 11. Middle East Respiratory Syndrome Coronavirus P Supporting Information AK 85 39 12. West Nile P Author Information AK 86 40 13. Hepatitis D and A P Corresponding Author AK 87 41 14. Rotavirus Q Present Address AK 88 42 15. Shingles Q Notes AK 89 43 16. Herpes Simplex Virus R Biographies AK 90 44 17. Ebola Virus S Acknowledgments AL 91 45 17.1. Description of EBOV S References AL 92 46 18. Marine Drugs for the Treatment of HIV/AIDS T 47 18.1. Phlorotannins V 48 18.2. Chitin, Chitosan, and Chitooligosaccharide 49 Derivatives V Received: November 2, 2013 50 18.3. Sulfated Polysaccharides W © XXXX American Chemical Society A DOI: 10.1021/cr4006318 Chem. Rev. XXXX, XXX, XXX−XXX Chemical Reviews Review 1. INTRODUCTION HIV and the resulting AIDS-associated infections have 122 7 become an international epidemic, resulting in over 30 million 123 93 Mammals have complex biological systems and are constantly 8 AIDS-related deaths worldwide. In 2011, around 2.5 million 124 94 prone to infections by a wide array of bacteria, fungi, viruses, and people were diagnosed with HIV, and an estimated 1.7 million 125 men, women, and children died from the complications of AIDS. 126 Around 34 million people were living with HIV by the end of 127 2011, with 69% of those infected in Sub-Saharan Africa. 128 Following Sub-Saharan Africa, the regions most affected with 129 HIV are the Caribbean, Eastern Europe, and Central Asia, where 130 7 1% of infected adults were living in 2011. 131 In Asia, it is estimated that at least 4.8 million people are 132 currently living with HIV, with China accounting for 780 000 of 133 those infected individuals followed by Thailand and Indonesia. 134 Eastern Europe and Latin America each has around 1.4 million 135 9 infected people. 136 In the United States, more than half a million people have died 137 10 − from AIDS-related complications, and it has been estimated 138 3 5 7 Figure 1. Mortality versus viral diseases. that over 1.3 million people are infected with HIV, some of 139 11 whom may not even be aware of their infection status. Those at 140 greatest risk for infection include individuals engaged in high-risk 141 12 behaviors, such as intravenous drug use. During 2007, in the 142 United States, HIV was the fourth leading cause of death for 143 Latinos and Hispanics between the ages of 35−44 and the sixth 144 13 leading cause of death between the ages of 25−34. According 145 14 to the National HIV/AIDS strategy, HIV and AIDS are most 146 commonly seen among African Americans. AIDS was first 147 documented by the United States CDC in 1982, in two females, 148 one Latina and the other African American. The epidemic of 149 AIDS began to spread among the African American population 150 15 from this point forward. 151 2.1. Nomenclature of HIV/AIDS − 6 Figure 2. Incidence rates versus viral diseases.3 5 The first instances of AIDS can be traced back to 1981, when a 152 strange illness began occurring in the homosexual communities; 153 however, the pandemic is reported to have started in the late 154 95 parasites, a significant challenge to the constant development of 16 1 1970s originating in Africa. In 1982, AIDS had different names 155 96 disease-strains resistance to current drugs. As a result, there is that included gay cancer, gay-related immune deficiency 156 97 always a need to identify new anti-infective agents against these 17 18 (GRID), gay compromise syndrome, and community- 157 98 organisms. An anti-infective agent is defined by Webster as “an acquired immune dysfunction. The term AIDS derived its 158 99 agent capable of acting against an infection, by inhibiting the 19 acronym in July 1982, at a meeting in Washington, DC. Initially 159 100 spread of an infectious agent or by killing the infectious agent 2 it was thought to be the disease of the “four H club” that included 160 101 outright”. Some of the emerging and drug-resistant infectious 16 heroin addicts, hemophiliacs, homosexuals, and Haitians. 161 102 diseases having research priority are human immunodeficiency The virus that was known to cause AIDS was initially named as 162 103 virus (HIV) or AIDS, hepatitis B and C viruses, respiratory 16 lymphadenopathy-associated virus, or LAV, in May 1983. On 163 104 infections such as influenza and respiratory syncytial virus (RSV), 1 April 23, it was announced that the virus known to cause AIDS 164 f1f2 105 and dengue fever. Figures 1 and 2 provide us with the data in was isolated and was named Human T-cell Leukemia Virus-III 165 106 regards to the mortality and incidence rates, respectively, of 3−5 (HTLV-III). It was thought that the LAV and HTLV-III could be 166 107 people with viral diseases. 20 the same virus. In March 1985, the United States Food and 167 108 Search engines utilized to identify the literature reviewed here fi Drug Administration (FDA) licensed the first blood test for 168 109 include Google scholar, Sci nder, Pubmed, government docu- 21 AIDS created by Abbott Laboratories to identify possible 169 110 ments from the CDC, NIH, and the World Health Organization 22 antibodies (for HIV). The name HIV or Human Immunode- 170 111 (WHO), academic journals, and books. ficiency Virus was given by the International Commission on 171 16 2. HUMAN IMMUNODEFICIENCY VIRUS Virological Nomenclature in May 1986. 172 112 DEMOGRAPHICS 2.2. Emergence of Drugs From Marine Sources 113 HIV-1 and HIV-2 can infect humans and cause severe Nature plays an important role in the generation of unique drug 173 + 114 immunosuppression through depletion of CD4 cells. HIV-2 prototypes of which about 60% of anticancer agents are derived 174 115 was first isolated in West Africa in 1986, and its mode of from natural sources and around 95% of the earth’s biosphere are 175 23 116 transmission is similar to HIV-1 except that it is generally less represented by the marine ecosystem. Hence, marine sources 176 117 infectious and the disease develops more slowly and is milder. As can be an invaluable source for the discovery of new compounds 177 118 the disease progresses, there are more infections with shorter for the treatment of diseases like AIDS or cancer. As an example, 178 24 119 durations compared to that of HIV-1. HIV-2 is seen three compounds, spongosine, spongothymidine, and spon- 179 25 120 predominately in Africa, but increasing incidences have been gouridine, were isolated from Cryptotethia crypta, a Caribbean 180 6 121 documented in the United States since 1987. marine sponge. These compounds were some of the first 181 B DOI: 10.1021/cr4006318 Chem.