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Review
. 2015 Sep 23;115(18):9655-706.
doi: 10.1021/cr4006318. Epub 2015 Aug 28.

Role of Marine Natural Products in the Genesis of Antiviral Agents

Vedanjali Gogineni  1 , Raymond F Schinazi  2 , Mark T Hamann  1
Affiliations
Review

Role of Marine Natural Products in the Genesis of Antiviral Agents

Vedanjali Gogineni et al. Chem Rev. .

Abstract

PubMed Disclaimer

Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Mortality versus viral diseases.–
Figure 2
Figure 2
Incidence rates versus viral diseases.–
Figure 3
Figure 3
Anti-HIV-1 drugs referenced in the history. Compounds include saquinavir (7), nevirapine (9), raltegravir (12), maraviroc (13), cobicistat (14), and fuzeon (15).
Figure 4
Figure 4
Structure of HIV.
Figure 5
Figure 5
Schematic representation of the virus replication cycle.
Figure 6
Figure 6
Crystal structures of HIV reverse transcriptase, integrase, RNA polymerase, and protease and scanning electron micrograph of HIV. Courtesy: National Institute of Allergy and Infectious Diseases, http://www.nih.gov/science/hiv/.
Figure 7
Figure 7
NNRTIs used for the treatment of HIV that include rilpivirine (17), etravirine (18), efavirenz (19), and delavirdine (20).
Figure 8
Figure 8
Various NRRIs possessing anti-HCV activity. NRRIs include valopicitabine (21), 2′-C-methyladenosine (22), 7-deaza-7-fluoro-2′-C-methyladenosine (23), 2′-O-methylcytidine (24), 7-deaza-2′-C-methyladenosine (25), 2′-C-methylguanosine (26), 4′-azidocytidine (27), 2′-deoxy-2′-fluoro-2′-C-methylcytidine (28), and R1626 (29).
Figure 9
Figure 9
Structure–activity relationship (SAR) of anti-HCV NRRIs.
Figure 10
Figure 10
Structures of ledipasvir (31), simeprevir (32), daclatasvir (33), ombitasvir (34), paritaprevir (35), and dasabuvir (36).
Figure 11
Figure 11
HIV protease inhibitors including amprenavir (37), indinavir (38), lopinavir (39), fosamprenavir (40), nelfinavir (41), darunavir (42), tipranavir (43), atazanavir (44), brecanavir (45), and ritonavir (46).
Figure 12
Figure 12
(A) HCV protease inhibitors that include boceprevir (47), telaprevir (48), ciluprevir (49), and SCH446211 (50). (B) HIV-1 entry inhibitors BMS-663068 (51) and cenicriviroc (52). (C) HIV-1 integrase inhibitors elvitegravir (53) and dolutegravir (54). (D) HIV-1 NNRTIs lersivirine (55) and dapivirine (56). (E) HIV-1 maturation inhibitor, Bevirimat (64).
Figure 13
Figure 13
Schematic representation of all the anti-HIV-1 drugs that act at various stages of viral replication cycle including the crystal structures of CD4 and CCR5.
Figure 14
Figure 14
Neuraminidase inhibitors: oseltamivir (66) and zanamivir (67); adamantane drugs: amantadine (68) and rimantadine (69).
Figure 15
Figure 15
Structure of hepatitis B virus with crystal structure of HBV e antigen and cryo-electron microscopy (CryoEM) structure of HBV core antigen.
Figure 16
Figure 16
Viral replication of Hepatitis B virus.
Figure 17
Figure 17
HBV drugs: adefovir dipivoxil (70), entecavir (71), telbivudine (72), clevudine (73), and thymosin (74).
Figure 18
Figure 18
Structure of RSV along with crystal structures of nucleoprotein, matrix protein, and fusion protein.
Figure 19
Figure 19
Chemical structure of ribavirin (75).
Figure 20
Figure 20
Structure of dengue virus along with the crystal structure of the envelope protein (E)
Figure 21
Figure 21
Structure of the SARS virus along with the crystal structures of spike glycoprotein, nucleocapsid phosphoprotein, and RNA.
Figure 22
Figure 22
Norovirus inhibitors: rupintrivir (76), favipiravir (77), suramin (78), 2′-C-methylcytidine (79), deubiquitinase [WP1130] (80), and elF4F inhibitors (81).
Figure 23
Figure 23
Structure of rotavirus along with the crystal structures of VP7, VP1, and VP6.
Figure 24
Figure 24
Structure of varicella-zoster virus (VZV).
Figure 25
Figure 25
Chemical structures of valacyclovir (82), acyclovir (83), and famciclovir (84).
Figure 26
Figure 26
Structure of HSV.
Figure 27
Figure 27
Chemical structures of idoxuridine (85) and phosphonoformate (86).
Figure 28
Figure 28
Structure of Ebola virus. Reprinted with permission from ref . Copyright 1989 American Chemical Society. Image from the RCSB PDB October 2014 Molecule of the Month featured by David Goodsell (DOI: 10.2210/rcsb_pdb/mom_2014_10)], crystal structures of glycoprotein, matrix proteins,, and electron scanning microscopic image (Courtesy: National Institute of Allergy and Infectious Diseases, http://www.niaid.nih.gov/news/newsreleases/2014/Pages/EbolaDisparities.aspx).
Figure 29
Figure 29
Schematic representation of the marine metabolites that are active at various stages of the viral replication cycle including the crystal structure of lectin.
Figure 30
Figure 30
Phlorotannins 8,8′-bieckol (87), 8,4‴-dieckol (88), and 6,6′-bieckol (89) isolated from a brown algae, Ecklonia cava, and diphlorethohydroxycarmalol (90) isolated from Ishige okamurae.
Figure 31
Figure 31
Sulfated chitin (91), chitosan (92), and chitooligosaccharide (93) derivatives.
Figure 32
Figure 32
Sulfated polysaccharides (94) isolated from red seaweeds.
Figure 33
Figure 33
Structure of laminaran (95).
Figure 34
Figure 34
Structures of Leu-Leu-Glu-Tyr-Ser-Ile (96) and Leu-Leu-Glu-Tyr-Ser-Leu (97).
Figure 35
Figure 35
Structures of polyphemusin I (98)–II (99) and tachyplesins I (100)–II (101).
Figure 36
Figure 36
Structures of macrolactin-A (102), Da-1 (103), and AcDa-1 (104).
Figure 37
Figure 37
Structures of equisetin (105) and phomasetin (106).
Figure 38
Figure 38
Structures of thalassiolins A (107), B (108), and C (109).
Figure 39
Figure 39
Structures of didemnaketals A (110) and B (111) and cyclodidemniserinol trisulfate (112).
Figure 40
Figure 40
Structure of lamellarin α 20-sulfate (113).
Figure 41
Figure 41
Avarol (114) and avarone (115) possessing anti-HIV-1 activity.
Figure 42
Figure 42
Curcuphenol (116) and its analogues a (117), c (118), j (119), and r (120) isolated and modified from the sponges Didiscus oxeata, Didiscus flavus, Myrmekioderma styx, and Epipolasis sp.
Figure 43
Figure 43
Papuamides A (121), B (122), C (123), and D (124) isolated from the marine sponges Theonella swinhoei and T. mirabilis.
Figure 44
Figure 44
Callipeltin A (125) isolated from Callipelta, neamphamide A (126) isolated from Neamphius huxleyi, mirabamide A (127), celebeside A (128), and theopapuamide B (129) isolated from Siliquariaspongia mirabilis.
Figure 45
Figure 45
Microspinosamide (130) isolated from the Indonesian sponge Sidonops microspinosa.
Figure 46
Figure 46
Dragmacidin F (131) isolated from the marine sponge belonging to the Halicortex genus from the southern coast of Ustica Island in Italy.
Figure 47
Figure 47
Manzamine A (132), 6-deoxymanzamine X (133), and 8-hydroxymanzamine (134) isolated from Haliclona sp.
Figure 48
Figure 48
Manadomanzamines A (135) and B (136) and xestomanzamine A (137) isolated from the Indonesian sponge Acanthostrongylophora sp.
Figure 49
Figure 49
Ptilomycalin A (139), isolated from the sponge Monanchora unguifera, and crambescidine 800 (138) and batzelladine C (140) isolated from the Batzella and Monanchora genera.
Figure 50
Figure 50
Isoaaptamine (141) and aaptamine (142) isolated from the sponge Aaptos aaptos.
Figure 51
Figure 51
Structures of petrosin (143) and petrosin A (144).
Figure 52
Figure 52
Cyanthiwigin B (145) isolated from the Jamaican sponge Epipolasis reiswigi.
Figure 53
Figure 53
Structures of haplosamates A (146) and B (147).
Figure 54
Figure 54
Structure of clathsterol (148).
Figure 55
Figure 55
Structure of polyacetylenetriol (149).
Figure 56
Figure 56
Structure of dehydrofurodendin (150).
Figure 57
Figure 57
Structure of the repeating unit of rosacelose (151).
Figure 58
Figure 58
Structure of sulfated polymannuroguluronate (SPMG) (152).
Figure 59
Figure 59
Structures of discorhabdins A (153) and C (154) and dihydrodiscorhabdin C (155).
Figure 60
Figure 60
Structures of ι- (156), λ- (157), and κ-carrageenans (158).
Figure 61
Figure 61
Structures of calyceramides A (159), B (160), and C (161).
Figure 62
Figure 62
Structures of weinbersterols A (162) and B (163) and stachyflin (164).
Figure 63
Figure 63
Structure of KCO (165).
Figure 64
Figure 64
Structures of dextran sulfate (166) and ulvan (167).
Figure 65
Figure 65
Structures of oligomeric mannuronic acid (OM) (168) and polymannuronic acid propyl sulfate (PMS) (169).
Figure 66
Figure 66
Structure of the carrageenan oligosaccharide CO-1 (170).
Figure 67
Figure 67
Structure of fucoidan (171).
Figure 68
Figure 68
Structures of halovirs A (172), B (173), C (174), D (175), and E (176).
Figure 69
Figure 69
Structures of eudistomins (177) and didemnins (178).
Figure 70
Figure 70
Structure of heparin (179).
Figure 71
Figure 71
Structure of μ-carrageenan (180).
Figure 72
Figure 72
Structures of mycalamide A (181), mycalamide B (182), 4-methylaaptamine (183), and hamigeran B (184).
Figure 73
Figure 73
HIV drugs in late stage development: GS 7340 (185), DPC 083 (186), SCH-C (187), S-1360 (188), T-1249 (189), MK-1439 (190), and S/GSK1265744 (191).
Figure 74
Figure 74
Novel HCV drugs: mericitabine (192), danoprevir (193), setrobuvir (194), BI 201335 (195), BI 207127 (196), MK-8742 (197), MK-5172 (198), MK-7009 or vaniprevir (199), and GSK 2336805 (200).
Figure 75
Figure 75
Structure of GS-9620 (201).
Figure 76
Figure 76
Structure of nitazoxanide (202).
Scheme 1
Scheme 1
Systematic Representation of the Chronological Order of HIV-1 and HCV Drugs Having Similar Structures to Ara-C, the First Anticancer Lead from a Sponge; All the Drugs and Compounds Mentioned in This Scheme Are NRTIs except for Dexelvucitabine (65), Which Is an HIV-1 Maturation Inhibitor, and Mericitabine (192), Which Is an HCV Nucleoside Inhibitor
Scheme 2
Scheme 2
Systematic Representation of the Chronological Order of HIV-1 and HCV Drugs Having Similar Nuclei to Ara-A, an Antiviral Agent; All the Drugs and Compounds Mentioned in This Scheme Are NRTIs
See this image and copyright information in PMC

References

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