Anti-HIV Activity of Extracts and Compounds from Algae and Cyanobacteria

doi:10.1006/eesa.1999.1862

Ecotoxicology and Environmental Safety

Volume 45, Issue 3, March 2000, Pages 208-227

https://doi.org/10.1006/eesa.1999.1862 Get rights and content

Abstract

The human immunodeficiency virus (HIV) is the retrovirus that causes the acquired immune deficiency disease syndrome (AIDS). This review discusses the anti-HIV activity of extracts and compounds isolated from freshwater and marine algae, and cyanobacteria (formerly called “blue-green algae”). Compounds and extracts with anti-HIV activity are also active against other retroviruses such as herpes simplex virus (HSV), but the amount of antiviral activity varies with the compound and the virus. Most of the research has focused on sulfated homopolysaccharides and heteropolysaccharides. Sulfoglycolipids, carrageenans, fucoidan, sesquiterpene hydroquinones, and other classes of compounds with anti-HIV activity that have been isolated from algae have received less attention. Most studies have used in vitro test systems, but a few in vivo studies have been carried out using compounds isolated from algae or analogs produced synthetically or isolated from other natural sources. Sulfated homopolysaccharides are more potent than sulfated heteropolysaccharides. The presence of the sulfate group is necessary for anti-HIV activity, and potency increases with the degree of sulfation. Studies using nonsulfated and sulfated homo- and heteropolysaccharides isolated from algae or other natural sources, or synthesized, have revealed the mechanisms of binding of drugs to the virion, and the mechanisms of viral binding to host cells. However, given the few classes of compounds investigated, most of the pharmacopeia of compounds in algae and cyanobacteria with antiretroviral activity is probably not known.

References (116)

M. Baba et al.
Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro
Antiviral Res.
(1988)
J. Balzarini et al.
The mannose-specific plant lectins from Cymbidium hybrid and Epipactis helleborine and the (N-acetylglucosamine)_n-specific plant lectin from Urtica dioica are potentent and selective inhibitors of human immunodeficiency virus and cytomegalovirus replication in vitro
Antiviral Res.
(1992)
D. Batinic et al.
The V3 region of the envelope glycoprotein of human immunodeficiency virus type 1 binds sulfated polysaccharides and CD₄-derived synthetic peptides
J. Biol. Chem.
(1992)
M.J. Carlucci et al.
Antiherpetic and anticoagulant properties of carrageenans from the red seaweed Gigartina skottsbergii and their cyclized derivatives: Correlation between structure and biological activity
Int. J. Biol. Macromol.
(1997)
G.A. Codd
Cyanobacterial toxins: Occurrence properties and biological significance
Water Sci. Technol.
(1995)
E.B. Damonte et al.
Antiviral activity of a sulfated polysaccharide from the red seaweed Nothogenia fastigiata
Biochem. Pharmacol.
(1994)
C.J. Elias et al.
Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan
Contraception
(1997)
K.R. Gustafson et al.
Isolation, primary sequence determination, and disulfide bond structure of cyanovirin-N, an anti-HIV (human immunodeficiency virus) protein from the cyanobacterium Nostoc ellipsosporum
Biochem. Biophys. Res. Commun.
(1997)
M. Hasui et al.
In vitro antiviral activities of sulfated polysaccharides from a marine microalga (Cochlodinium polykrikoides) against human immunodeficiency virus and other enveloped viruses
Int. J. Biol. Macromol.
(1995)
L.M. Hiebert et al.
Orally administered dextran sulfate is absorbed in HIV-positive individuals
J. Lab. Clin. Med.
(1999)

P.P. Jagodzinski et al.

Mechanism of the inhibitory effect of curdlan sulfate on HIV-1 infection in vitro

Virology

(1994)

A.A. Kolender et al.

The system of sulfated alpha-(1→3)-linked $D$ -mannans from the red seaweed Nothogenia fastigiata: Structures, antitherpetic and anticoagulant properties

Carbohydr. Res.

(1997)

S. Loya et al.

Peyssonols A and B, two novel inhibitors of the reverse transcriptases of human immunodeficiency virus types 1 and 2

Arch. Biochem. Biophys.

(1995)

J.M. Mariner et al.

The HIV-inactivating protein, cyanovirin-N, does not block gp120-mediated virus-to-cell binding

Biochem. Biophys. Res. Commun.

(1998)

M.C. Matulewicz et al.

Water-soluble sulfated polysaccharides from the red seaweed Chaetangium fatigiatum. Analysis of the system and structures of the α- $D$ -(1→3)-linked mannans

Carbohyd. Pol.

(1987)

T. Mori et al.

Recombinant production of cyanovirin-N, a potent human immunodeficiency virus-inactivating protein derived from a cultured cyanobacterium

Protein Expr. Purif.

(1998)

T. Mori et al.

Analysis of sequence requirements for biological activity of cyanovirin-N, a potent HIV (human immunodeficiency virus)-inactivating protein

Biochem. Biophys. Res. Commun.

(1997)

T. Mori et al.

Construction and enhanced cytotoxicity of a [cyanovirin-N]-[Pseudomonas exotoxin] conjugate against human immunodeficiency virus-infected cells

Biochem. Biophys. Res. Commun.

(1997)

R. Pratt et al.

Report on antibiotic activity of seaweed extracts

J. Am. Pharm. Assoc.

(1951)

D. Abrams et al.

A phase I/II dose ranging trial of oral dextran sulfate in HIV p24 antigen positive individuals (ACTG 060): Results of a safety and efficacy trial

Int. Conf. AIDS

(1989)

D.I. Abrams et al.

Oral dextran sulfate (UA001) in the treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex

Ann. Intern. Med.

(1989)

R. Anand et al.

Sodium pentosan polysulfate (SP-54), an anti-HIV agent also exhibits lymphocyte proliferative activity and synergism with AZT

Int. Conf. AIDS

(1989)

R. Anand et al.

Sodium pentosan polysulfate (PPS), an anti-HIV agent also exhibits synergism with AZT, lymphoproliferative activity, and virus enhancement

AIDS Res. Hum. Retroviruses

(1990)

R. Anand et al.

The sulfated sugar alpha-cyclodextrin sulfate (α-CDS) is a potent anti-HIV agent, has marked synergism with AZT, and exhibits lymphoproliferative activity

Int. Conf. AIDS

(1990)

S. Ayehunie et al.

Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis)

J. Acquir. Immune. Defic. Syndr. Hum. Retrovirol.

(1998)

M. Baba et al.

Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus

Antimicrob. Agents Chemother.

(1988)

M. Baba et al.

Comparative inhibitory effects of sulfated polysaccharides on giant cell formation induced by co-cultivation of CD₄-positive cells with persistently HIV-1-infected cells

Int. Conf. AIDS

(1989)

M. Baba et al.

Sulfated polysaccharides as potent inhibitors of HIV-induced syncytium formation: A new strategy towards AIDS chemotherapy

J. Acquir. Immune. Defic. Syndr.

(1990)

O. Bagasra et al.

Anti-HIV-1 activities of sulfated monosaccharides (SMS) and polysaccharides (SPS): Therapeutic indices (TI)

Int. Conf. AIDS

(1989)

O. Bagasra et al.

Anti-human immunodeficiency virus type 1 activity of sulfated monosaccharides: comparison with sulfated polysaccharides and other polyions

J. Infect. Dis.

(1991)

M. Balter

Revealing HIV's T cell passkey

Science

(1998)

A. Beress et al.

A new procedure for the isolation of anti-HIV compounds (polysaccharides and polyphenols) from the marine alga Fucus vesiculosus

J. Nat. Prod.

(1993)

C.A. Bewley et al.

Solution structure of cyanovirin-N, a potent HIV-inactivating protein

Nat. Struct. Biol.

(1998)

M.R. Boyd et al.

Discovery of cyanovirin-N, a novel HIV-inactivating protein from Nostoc ellipsosporum that targets viral gp120

Int. Conf. AIDS

(1996)

M.R. Boyd et al.

Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development

Antimicrob. Agents Chemother.

(1997)

P.R. Burkholder et al.

Antimicrobial agents from the sea

Lloydia

(1969)

J.H. Cardellina et al.

A chemical screening strategy for the dereplication and prioritization of HIV-inhibitory aqueous natural products extracts

J. Nat. Prod.

(1993)

M.J. Carlucci et al.

Antiviral activity of natural sulphated galactans on herpes virus multiplication in cell culture

Planta Med.

(1997)

G. Chamorro et al.

Pharmacology and toxicology of Spirulina alga

Rev. Invest. Clin.

(1996)

E.B. Damonte

Antiviral agents that act in the early phases of the viral cycle

Rev. Argent. Microbiol.

(1996)

E.B. Damonte et al.

Herpes simplex virus-inhibitory sulfated xylogalactans from the red seaweed Nothogenia fastigiata

Chemotheraphy

(1996)

E. De Clercq

Selective virus inhibitors

Microbiologica

(1990)

E.F. Deig

Inhibition of herpes virus replication by marine algae extracts

Antimicrob. Agents Chemother.

(1974)

D.W. Ehresmann et al.

Antiviral substances from California marine algae

J. Phycol.

(1977)

M.T. Esser et al.

Cyanovirin-N binds to gp120 to interfere with CD₄-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD₄ binding site on gp120 or soluble CD₄-induced conformational changes in gp120

J. Virol.

(1999)

R. Filalimouhim et al.

Antiviral activities of sulfated polysaccharides

Acta Botanica Gallica

(1995)

C. Flexner et al.

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection

Antimicrob. Agents Chemother.

(1991)

G.E. Fogg

The Metabolism of Algae

(1953)

P. Gerber et al.

Protective effect of seaweed extracts for chicken embryos infected with influenza B or mumps

Proc. Soc. Exp. Biol. Med.

(1958)

M.E. Gonzalez et al.

Polysaccharides as antiviral agents: Antiviral activity of carrageenan

Antimicrob. Agents Chemother.

(1987)

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ReviewAnti-HIV Activity of Extracts and Compounds from Algae and Cyanobacteria

Abstract

Antiviral Res.

Antiviral Res.

J. Biol. Chem.

Int. J. Biol. Macromol.

Water Sci. Technol.

Biochem. Pharmacol.

Contraception

Biochem. Biophys. Res. Commun.

Int. J. Biol. Macromol.

J. Lab. Clin. Med.

Virology

Carbohydr. Res.

Arch. Biochem. Biophys.

Biochem. Biophys. Res. Commun.

Carbohyd. Pol.

Protein Expr. Purif.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

J. Am. Pharm. Assoc.

A phase I/II dose ranging trial of oral dextran sulfate in HIV p24 antigen positive individuals (ACTG 060): Results of a safety and efficacy trial

Int. Conf. AIDS

Oral dextran sulfate (UA001) in the treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex

Ann. Intern. Med.

Sodium pentosan polysulfate (SP-54), an anti-HIV agent also exhibits lymphocyte proliferative activity and synergism with AZT

Int. Conf. AIDS

Sodium pentosan polysulfate (PPS), an anti-HIV agent also exhibits synergism with AZT, lymphoproliferative activity, and virus enhancement

AIDS Res. Hum. Retroviruses

The sulfated sugar alpha-cyclodextrin sulfate (α-CDS) is a potent anti-HIV agent, has marked synergism with AZT, and exhibits lymphoproliferative activity

Int. Conf. AIDS

Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis)

J. Acquir. Immune. Defic. Syndr. Hum. Retrovirol.

Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus

Antimicrob. Agents Chemother.

Comparative inhibitory effects of sulfated polysaccharides on giant cell formation induced by co-cultivation of CD4-positive cells with persistently HIV-1-infected cells

Int. Conf. AIDS

Sulfated polysaccharides as potent inhibitors of HIV-induced syncytium formation: A new strategy towards AIDS chemotherapy

J. Acquir. Immune. Defic. Syndr.

Anti-HIV-1 activities of sulfated monosaccharides (SMS) and polysaccharides (SPS): Therapeutic indices (TI)

Int. Conf. AIDS

Anti-human immunodeficiency virus type 1 activity of sulfated monosaccharides: comparison with sulfated polysaccharides and other polyions

J. Infect. Dis.

Revealing HIV's T cell passkey

Science

A new procedure for the isolation of anti-HIV compounds (polysaccharides and polyphenols) from the marine alga Fucus vesiculosus

J. Nat. Prod.

Solution structure of cyanovirin-N, a potent HIV-inactivating protein

Nat. Struct. Biol.

Discovery of cyanovirin-N, a novel HIV-inactivating protein from Nostoc ellipsosporum that targets viral gp120

Int. Conf. AIDS

Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development

Antimicrob. Agents Chemother.

Antimicrobial agents from the sea

Lloydia

A chemical screening strategy for the dereplication and prioritization of HIV-inhibitory aqueous natural products extracts

J. Nat. Prod.

Antiviral activity of natural sulphated galactans on herpes virus multiplication in cell culture

Planta Med.

Pharmacology and toxicology of Spirulina alga

Rev. Invest. Clin.

Antiviral agents that act in the early phases of the viral cycle

Rev. Argent. Microbiol.

Herpes simplex virus-inhibitory sulfated xylogalactans from the red seaweed Nothogenia fastigiata

Chemotheraphy

Selective virus inhibitors

Microbiologica

Inhibition of herpes virus replication by marine algae extracts

Antimicrob. Agents Chemother.

Antiviral substances from California marine algae

J. Phycol.

Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120

J. Virol.

Antiviral activities of sulfated polysaccharides

Acta Botanica Gallica

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection

Antimicrob. Agents Chemother.

The Metabolism of Algae

Protective effect of seaweed extracts for chicken embryos infected with influenza B or mumps

Proc. Soc. Exp. Biol. Med.

Review
Anti-HIV Activity of Extracts and Compounds from Algae and Cyanobacteria

Comparative inhibitory effects of sulfated polysaccharides on giant cell formation induced by co-cultivation of CD₄-positive cells with persistently HIV-1-infected cells

Cyanovirin-N binds to gp120 to interfere with CD₄-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD₄ binding site on gp120 or soluble CD₄-induced conformational changes in gp120