Mechanism of the Antiviral Activity of New Aurintricarboxylic Acid Analogues

Reymen, D.; Witvrouw, Myriam; Ballana, Ester; Neyts, Johan; Schols, Dominique; Andrei, Gracíela; Snoeck, Robert; Cushman, Mary; Hejchman, Elżbieta; Clercq, Erik De

doi:10.1177/095632029600700304

Cited by 14 publications

(13 citation statements)

References 32 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is likely that the polycarboxylates in the current investigation exert their activity against HSV in a similar fashion, although detailed studies are required. Previous studies on poly(hydroxy)carboxylates did demonstrate that the antiviral effects of polymers are dependent on their molecular weight and the number of carboxylic acid groups present in the polymer. , Our results are in congruence with these reports. Among phthalate-terminated polymers, PVAP showed the highest activity against HSV-1 that was significant even at a concentration of 50 μg/mL.…”

Section: Discussionsupporting

confidence: 92%

“…While the mechanism of action of polycarboxylates against HIV has been well-studied in the past, their mode of action against HSV remains relatively underexplored. Previous studies on poly(hydroxy)carboxylates suggest that polycarboxylates could interact with cationic domains of HSV glycoproteins gB and gC which will further prevent the interaction of the HSV with heparan sulfate proteoglycans on the cell surface …”

mentioning

confidence: 99%

See 1 more Smart Citation

Pharmaceutically Acceptable Carboxylic Acid-Terminated Polymers Show Activity and Selectivity against HSV-1 and HSV-2 and Synergy with Antiviral Drugs

et al. 2020

View full text Add to dashboard Cite

Polyanionic macromolecules including carboxylate-terminated polymers (polycarboxylates) are capable of inhibiting sexually transmitted viruses such as human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Cellulose acetate phthalate (CAP), a pharmaceutically acceptable pH-sensitive polycarboxylate polymer, showed promising prophylactic activity against HIV and HSV, but the instability of CAP in an aqueous environment prevented its clinical development. Interestingly, several pharmaceutically acceptable polycarboxylates have features similar to CAP with an aqueous stability significantly higher than that of CAP. However, their activity against sexually transmitted viruses remains unexplored. Here, we evaluate the activity of various polycarboxylates such as polyvinyl acetate phthalate (PVAP), various grades of hydroxypropyl methylcellulose phthalate (HPMCP-50, HPMCP-55, and HPMCP-55S), and various grades of methacrylic acid copolymers (Eudragit L100-55, Eudragit L100, Eudragit S100, and Kollicoat MAE 100P) against HSV. We, for the first time, demonstrate that PVAP, HPMCP-55S, and Eudragit S100 have activity and selectivity against HSV-1 and HSV-2. Further, we report that polycarboxylates can be easily transformed into nanoparticles (NPs) and in the nanoparticulate form, they show similar or enhanced activity against HSV. Finally, using PVAP NPs, as a model, we demonstrate using in vitro HSV therapy studies that polycarboxylate NPs are capable of synergizing with antiviral drugs such as acyclovir (ACV), tenofovir, and tenofovir disoproxil fumarate. Thus, pharmaceutically acceptable carboxylic acid-terminated polymers and their NPs have the potential to be developed into topical formulations for the prevention and treatment of HSV infection.

show abstract

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Pharmaceutically Acceptable Carboxylic Acid-Terminated Polymers Show Activity and Selectivity against HSV-1 and HSV-2 and Synergy with Antiviral Drugs

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Besides ions, other antiviral moieties have been studied. Aurintricarboxylic acid (ATA) could easily be polymerized in water by reacting salicylic acid with formaldehyde, sulphuric acid, and sodium nitrite [49]. Reymen et al displayed that owing to an interaction between aurintricarboxylic acid analog polymers and the virus membrane/envelope, the replication of DNA and RNA virus was inhibited [49].…”

Section: Introductionmentioning

confidence: 99%

“…Aurintricarboxylic acid (ATA) could easily be polymerized in water by reacting salicylic acid with formaldehyde, sulphuric acid, and sodium nitrite [49]. Reymen et al displayed that owing to an interaction between aurintricarboxylic acid analog polymers and the virus membrane/envelope, the replication of DNA and RNA virus was inhibited [49]. Sulphate and phosphorothioate oligonucleotides have been studied for antiviral therapeutics, due to their effect on the hydrophobic properties of the virus envelops, affecting the virus penetrating ability.…”

Section: Introductionmentioning

confidence: 99%

Polymers in the Medical Antiviral Front-Line

2020

View full text Add to dashboard Cite

Antiviral polymers are part of a major campaign led by the scientific community in recent years. Facing this most demanding of campaigns, two main approaches have been undertaken by scientists. First, the classic approach involves the development of relatively small molecules having antiviral properties to serve as drugs. The other approach involves searching for polymers with antiviral properties to be used as prescription medications or viral spread prevention measures. This second approach took two distinct directions. The first, using polymers as antiviral drug-delivery systems, taking advantage of their biodegradable properties. The second, using polymers with antiviral properties for on-contact virus elimination, which will be the focus of this review. Anti-viral polymers are obtained by either the addition of small antiviral molecules (such as metal ions) to obtain ion-containing polymers with antiviral properties or the use of polymers composed of an organic backbone and electrically charged moieties like polyanions, such as carboxylate containing polymers, or polycations such as quaternary ammonium containing polymers. Other approaches include moieties hybridized by sulphates, carboxylic acids, or amines and/or combining repeating units with a similar chemical structure to common antiviral drugs. Furthermore, elevated temperatures appear to increase the anti-viral effect of ions and other functional moieties.

show abstract

“…5,6 It inhibits both the attachment of gp120 to CD4 as well as an undefined postattachment event prior to reverse transcription. 7 Attempts to improve the potency of cosalane (EC 50 : 5.1 µM vs HIV-1 RF in CEM-SS cells) have resulted in several series of cosalane analogues, including those derived from attachment of the disalicylmethane pharmacophore to various regions of the steroid 8 and from modification of the linker chain.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Anti-HIV Activity with Anion Spacing in a Series of Cosalane Analogues with Extended Polycarboxylate Pharmacophores

et al. 2001

View full text Add to dashboard Cite

Cosalane and its synthetic derivatives inhibit the binding of gp120 to CD4 as well as the fusion of the viral envelope with the cell membrane. The binding of the cosalanes to CD4 is proposed to involve ionic interactions of the negatively charged carboxylates of the ligands with positively charged arginine and lysine amino acid side chains of the protein. To investigate the effect of anion spacing on anti-HIV activity in the cosalane system, a series of cosalane tetracarboxylates was synthesized in which the two proximal and two distal carboxylates are separated by 6--12 atoms. Maximum activity was observed when the proximal and distal carboxylates are separated by 8 atoms. In a series of cosalane amino acid derivatives containing glutamic acid, glycine, aspartic acid, beta-alanine, leucine, and phenylalanine residues, maximum activity was displayed by the di(glutamic acid) analogue. A hypothetical model has been devised for the binding of the cosalane di(glutamic acid) conjugate to CD4. In general, the compounds in this series are more potent against HIV-1(RF) in CEM-SS cells than they are vs HIV-1(IIIB) in MT-4 cells, and they are least potent vs HIV-2(ROD) in MT-4 cells.

show abstract

Mechanism of the Antiviral Activity of New Aurintricarboxylic Acid Analogues

Cited by 14 publications

References 32 publications

Pharmaceutically Acceptable Carboxylic Acid-Terminated Polymers Show Activity and Selectivity against HSV-1 and HSV-2 and Synergy with Antiviral Drugs

Pharmaceutically Acceptable Carboxylic Acid-Terminated Polymers Show Activity and Selectivity against HSV-1 and HSV-2 and Synergy with Antiviral Drugs

Polymers in the Medical Antiviral Front-Line

Correlation of Anti-HIV Activity with Anion Spacing in a Series of Cosalane Analogues with Extended Polycarboxylate Pharmacophores

Contact Info

Product

Resources

About