Polyacetal Carboxylic Acids: a New Group of Antiviral Polyanions

Claes, P.; Billiau, Alfons; Clercq, Erik De; Desmyter, Jan; Schonne, E.; Vanderhaeghe, Hubert; Somer, P. De

doi:10.1128/jvi.5.3.313-320.1970

Cited by 75 publications

(34 citation statements)

References 16 publications

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“…An adequate, protective effect with COAM is achieved only when given prophylactically [16,26,38]. This seems logical, as in case of lethal mengovirus infection, the immunostimulatory capacity of COAM will likely surpass a direct viral inhibitory effect [20], which may explain why preventive administration is more efficient, as innate immune effector cells can be trig- gered promptly to sustain an efficient antiviral response.…”

Section: Discussionmentioning

confidence: 99%

“…COAM was synthesized, purified, and fractionated according to MW as described [20,26]. It was endotoxin-free, as tested by the Limulus amebocyte lysate test.…”

Section: Reagentsmentioning

confidence: 99%

“…Endotoxin-free and chemically stable COAM was synthesized and fractionated as described [20,26]. When we compared the antiviral effects of COAM and polyI:C against lethal mengovirus infection, polyI:C, at a dose of 0.5 mg injected i.p.…”

Section: Coam Rescues From Lethal Virus Infectionmentioning

confidence: 99%

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Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection

Starckx

Martens

et al. 2010

Journal of Leukocyte Biology

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Insight into molecular and cellular mechanisms of innate immunity is critical to understand viral pathogenesis and immunopathology and might be exploited for therapy. Whereas the molecular mechanisms of the IFN defense are well established, cellular mechanisms of antiviral immunity are only emerging, and their pharmacological triggering remains unknown. COAM is a polysaccharide derivative with antiviral activity but without comprehension about its mechanism of action. The COAM mixture was fractionated, and prophylactic treatment of mice with COAM polymers of high MW resulted in a conversion from 100% lethal mengovirus infection to an overall survival rate of 93% without obvious clinical sequelae. Differential and quantitative analysis of peritoneal leukocytes demonstrated that COAM induced a profound influx of neutrophils. Selective cell depletion experiments pointed toward neutrophils and macrophages as key effector cells in the rescue of mice from lethal mengovirus. COAM was able to induce mRNA and protein expression of the mouse neutrophil chemokine GCP-2. Binding of GCP-2 to COAM was demonstrated in solution and confirmed by SPR technology. Although COAM was not chemotactic for neutrophils, COAM-anchored muGCP-2 retained chemotactic activity for human and mouse neutrophils. In conclusion, this study established that COAM rescued mice from acute and lethal mengovirus infection by recruiting antiviral leukocytes to the site of infection, as proposed through the induction, binding, and concentration of endogenous chemokines. These findings reinforce the role of neutrophils and macrophages as critical cells that can be manipulated toward antiviral defense.

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Section: Discussionmentioning

confidence: 99%

“…COAM was synthesized, purified, and fractionated according to MW as described [20,26]. It was endotoxin-free, as tested by the Limulus amebocyte lysate test.…”

Section: Reagentsmentioning

confidence: 99%

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Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection

Starckx

Martens

et al. 2010

Journal of Leukocyte Biology

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“…Many of the agents that protect against B. microti have been reported to induce interferon. Thus COAM (Claes et al 1970), C. parvum (Kirchner et al 1977), B. abortus (Younger & Stinebring 1964), some Salmonellae (Stinebring & Younger 1964) and Listeria monocytogenes (Lukas & Hruskova 1967) all induce interferon, whereas Staphylococcus sp., which did not protect, has been tested as an interferon inducer without success (Ho & Armstrong 1975). While there appear to be no reports for zymosan, mannan, another fungal polysaccharide, induces interferon (Borecky et al 1967).…”

Section: Discussionmentioning

confidence: 99%

Protection of mice against Babesia microti with cord factor, COAM, zymosan, glucan, Salmonella and Listeria

Clark

1979

Parasite Immunology

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Cord factor (trehalose 6-6' dimycolate). COAM (chlorite-oxidized oxyamylose), zymosan, glucan, Salmonella enteritidis 11RX and Listeria monocytogenes were found to protect mice against subsequent infection with Babesia microti, an intra-erythrocytic protozoan parasite. This protection was not observed after injection of Staphylococcus epidermidis, a viridans group Streptococcus, thioglycollate, or colloidal carbon. All the agents which protect against B. microti have also been reported to induce non-specific protection against experimental tumours. The parasites appear to die inside circulating red cells. This implies that these can exert non-specific protection against this parasite through the mediation of a soluble factor.

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“…In the scope of designing polyanionic substances, such as polycarboxylic acids, as inducers of interferon, we synthesized polyacrylic acid, polymethylacrylic acid 9-(2phosphonylmethoxy)ethyl)adenine, and chlorite-oxidized oxyamylose. [5][6][7] These polyanions not only stimulated interferon production but could also exhibit antiviral effects through various other mechanisms. Thus, a synthetic program was started in collaboration with Prof. G. Smets, Leuven's polymer authority, that led to the synthesis of the polyampholyte (PEA) ( Fig.…”

Section: A Polyethylene Alanine (Pea)mentioning

confidence: 99%

Curious Discoveries in Antiviral Drug Development: The Role of Serendipity

Clercq

2015

Med. Res. Rev.

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Antiviral drug development has often followed a curious meandrous route, guided by serendipity rather than rationality. This will be illustrated by ten examples. The polyanionic compounds (i) polyethylene alanine (PEA) and (ii) suramin were designed as an antiviral agent (PEA) or known as an antitrypanosomal agent (suramin), before they emerged as, respectively, a depilatory agent, or reverse transcriptase inhibitor. The 2',3'-dideoxynucleosides (ddNs analogues) (iii) have been (and are still) used in the "Sanger" DNA sequencing technique, although they are now commercialized as nucleoside reverse transcriptase inhibitors (NRTIs) in the treatment of HIV infections. (E)-5-(2-Bromovinyl)-2'-deoxyuridine (iv) was discovered as a selective anti-herpes simplex virus compound and is now primarily used for the treatment of varicella-zoster virus infections. The prototype of the acyclic nucleoside phosphonates (ANPs), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (v) was never commercialized, although it gave rise to several marketed products (cidofovir, adefovir, and tenofovir). 1-[2-(Hydroxyethoxy)methyl]-6-(phenylthio)thymine (vi) and TIBO (tetrahydroimidazo[4,5,1-jk][1,4-benzodiazepin-2(1H)]-one and -thione) (vii) paved the way to a number of compounds (i.e., nevirapine, delavirdine, etravirine, and rilpivirine), which are now collectively called non-NRTIs. The bicyclam AMD3100 (viii) was originally described as an anti-HIV agent before it became later marketed as a stem cell mobilizer. The S-adenosylhomocysteine hydrolase inhibitors (ix), while active against a broad range of (-)RNA viruses and poxviruses may be particularly effective against Ebola virus, and for (x) the O-ANP derivatives, the potential application range encompasses virtually all DNA viruses.

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Polyacetal Carboxylic Acids: a New Group of Antiviral Polyanions

Cited by 75 publications

References 16 publications

Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection

Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection

Protection of mice against Babesia microti with cord factor, COAM, zymosan, glucan, Salmonella and Listeria

Curious Discoveries in Antiviral Drug Development: The Role of Serendipity

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