Antiherpetic activity and mode of action of natural carrageenans of diverse structural types

Carlucci, MJ; Ciancia, Marina; Matulewicz, Marı́a C.; Cerezo, Alberto S.; Damonte, Elsa B.

doi:10.1016/s0166-3542(99)00038-8

Cited by 146 publications

(123 citation statements)

References 30 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…However, it is not known whether this activity was due to disruption of viral particles. Other sulfated oligo-and polysaccharides (8), including those used in microbicidal trials, i.e., cellulose sulfate (42), and some carrageenans (44) did not show strong virus-inacti- vating activity, implying, similar to the case with muparfostat, a reversible mode of antiviral activity. Such nonvirucidal binding of GAG mimetics may result in coating and protection of infectious virions against proteolytic degradation in the mucosal milieu (45), a known feature of the protein-GAG interaction (22).…”

Section: Discussionmentioning

confidence: 98%

The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles

Said

Trybala

Görander

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bHerpes simplex virus (HSV) and many other viruses, including HIV, initiate infection of host cells by binding to glycosaminoglycan (GAG) chains of cell surface proteoglycans. Although GAG mimetics, such as sulfated oligo-and polysaccharides, exhibit potent antiviral activities in cultured cells, the prophylactic application of these inhibitors as vaginal microbicides failed to protect women upon their exposure to HIV. A possible explanation for this failure is that sulfated oligo-and polysaccharides exhibit no typical virucidal activity, as their interaction with viral particles is largely electrostatic and reversible and thereby vulnerable to competition with GAG-binding proteins of the genital tract. Here we report that the cholestanol-conjugated sulfated oligosaccharide PG545, but not several other sulfated oligosaccharides lacking this modification, exhibited virucidal activity manifested as disruption of the lipid envelope of HSV-2 particles. The significance of the virus particle-disrupting activity of PG545 was also demonstrated in experimental animals, as this compound, in contrast to unmodified sulfated oligosaccharide, protected mice against genital infection with HSV-2. Thus, PG545 offers a novel prophylaxis option against infections caused by GAG-binding viruses. Since the original finding of WuDunn and Spear (1) that ubiquitous and negatively charged glycosaminoglycan (GAG) chains of cell surface proteoglycans provide the binding sites for attachment of herpes simplex virus (HSV) to cells, these oligosaccharides have been reported to assist infection of cells by a number of different viruses, including respiratory syncytial virus (RSV) (2, 3), HIV-1 (4), and Ebola virus (5). In HSV, glycoprotein C (gC) (6) and/or gB (7) mediates virus binding to cell surface GAGs. Sulfated polysaccharides and other polysulfonated compounds that mimic the structure of GAG chains are well-known inhibitors of the virus-GAG interaction in cultured cells (3,8,9). Due to extensive sulfonation, these compounds efficiently outcompete the binding of cell surface GAGs to the viral attachment proteins, thus preventing infection of cells. Notably, the same GAG mimetics can inhibit infectivity of different 9). In spite of potent antiviral activity in cultured cells, these inhibitors, i.e., cellulose sulfate, carrageenan, and PRO2000 (sulfonated poly-naphthalene), failed to protect women against contraction of HIV when tested as intravaginal virucides in several large clinical trials (10-12). Furthermore, there was an indication that one of these GAG mimetics, i.e., cellulose sulfate, increased the risk of contracting HIV (10). Although it is unclear why these compounds lack protective effects in humans (12, 13), some intrinsic features of the virus-GAG interaction, such as reversibility of the binding, may help to elucidate this issue. Virus binding to ubiquitous cell surface components, such as GAGs or sialic acid, has to be neatly balanced to avoid redundant dead-end interactions resulting in trapping of viral particles. Some...

show abstract

Section: Discussionmentioning

confidence: 98%

The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles

Said

Trybala

Görander

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In recent years, several classes of polysaccharides, including mannans, glucans, galactans, fucans, carrageenans, and their derivatives, especially their sulfated derivatives have been reported to possess antiviral activity against HSV (Carlucci et al, 1999). Our group also isolated a polysaccharide component named PD from Polygonatum cyrtonema Hua, a traditional Chinese medicinal herb.…”

Section: Introductionmentioning

confidence: 97%

Structure of polysaccharide from Polygonatum cyrtonema Hua and the antiherpetic activity of its hydrolyzed fragments

Liu

Meng

et al. 2004

Antiviral Research

View full text Add to dashboard Cite

“…This is reflected in the many investigations into their bioactivities such as antiangiogenic (Koyanagi et al, 2003), antitumor (Hiroishi et al, 2001;Zhou et al, 2004), anticoagulant (Chevolot et al, 1999), immunomodulating (Shan et al, 1999), antioxidant (Ahn et al, 2004;Zhang et al, 2004), antiviral (Boyd et al, 1997;Carlucci et al, 1999;Huheihel et al, 2002;Ahn et al, 2002), antiinflammatory (Jiang et al, 1999;Okai & Higashi-Okai, 1997), antimicrobial (Donia & Hamann, 2003;Haefner, 2003), hemagglutination (Kakita et al, 1999), and more.…”

Section: Introductionmentioning

confidence: 99%

Antimycobacterial Activity of the Red AlgaPolysiphonia virgata.

Saravanakumar

Folb

Campbell

et al. 2008

Pharmaceutical Biology

View full text Add to dashboard Cite

The red marine alga (Polysiphonia virgata C. Agardh; Rhodomelaceae) was investigated for antimycobacterial activity. Bioassay-guided fractionation of the dichloromethane algal extract using direct bioautography resulted in isolation of a mixture of long-chain fatty acids, namely oleic acid, linoleic acid, lauric acid, and myristic acid as the major antimycobacterial compounds. Oleic acid showed the greatest inhibition of the growth of Mycobacterium smegmatis with a minimum inhibitory quantity (MIQ) of 0.8 µg; linoleic acid and lauric acid had MIQ values of 1.56 and 3.125 µg, respectively. Stearic acid, palmitic acid, and myristic acid did not inhibit the growth of M. smegmatis. Using the Bactec-460 radiometric method, oleic acid showed 100% inhibition of the growth of Mycobacterium tuberculosis at a minimum inhibitory concentrations (MIC) of 25 µg/mL; lauric acid, myristic acid, and linoleic acid all showed 100% inhibition at MIC values of 50 µg/mL. Myristic acid and lauric acid showed 90% and 76% inhibition at 50 µg/mL. Linoleic acid showed moderate inhibition of the growth of a clinical strain of multidrug-resistant M. tuberculosis 50 µg/mL.

show abstract

Antiherpetic activity and mode of action of natural carrageenans of diverse structural types

Cited by 146 publications

References 30 publications

The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles

The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles

Structure of polysaccharide from Polygonatum cyrtonema Hua and the antiherpetic activity of its hydrolyzed fragments

Antimycobacterial Activity of the Red AlgaPolysiphonia virgata.

Contact Info

Product

Resources

About