Poly(Hydroxy)Carboxylates as Selective Inhibitors of Cytomegalovirus and Herpes Simplex Virus Replication

Abstract

SummaryPolyhydroxycarboxylates (MW 3800-14000) derived from phenolic (PDP) compounds were found to be selective inhibitors of human cytomegalovirus (CMV), herpes simplex Virus type 1 (HSV-1), type 2 (HSV-2), thymidine kinase-deficient (TK-c) HSV-1 and vaccinia virus replication at concentrations that are not toxic to the host cells. The PDP compounds were not inhibitory to parainfluenza virus, reovirus, Sindbis virus, or Semliki forest virus. The polycarboxylate aurintricarboxylic acid (ATA) (MW 1149-3336) also proved inhibitory to CMV and HSV replication. The anti-CMV and anti-HSV activities of the ATA polymers increased with increasing molecular weight. The mechanism of anti-CMV activity of both the PDP and ATA series of compounds can be attributed to the inhibition of virion attachment to the cells, probably due to an interaction of these polyanionic compounds with the positively charged domains of the viral envelope glycoproteins.

In vitro Activity of Polyhydroxycarboxylates against Herpesviruses and Hiv

“…The most antivirally effective phenolic polymers were the different salt forms of KOP (sodium-, ammonium-, potassium salt) as well as the copolymers containing KOP (KHYKOP, KGALOP). In previous studies Neyts et al (1992b) also reported inhibition of HSV and HCMV replication by the more simple polymers HYKOP and GALOP. They studied the inhibition of radiolabelled HCMV virions to the cells and demonstrated that KOP, GALOP and HYKOP are able to displace CMV virions that were bound to heparin immobilized on a Sepharose column.…”

“…Vero cells are green monkey kidney cells but impress morphologically like epithelial cells. Neyts et al (1992b) described a good antiviral activity of the first panel of polyhydroxycarboxylates with the skinmuscle cell line E 6 SM and the HSV-1 (KOS), TK -HSV-1 (B2006) and HSV-2 (G) virus strains. Findings with Vero cells and E 6 SM cells provide further evidence that polyhydroxycarboxylates are potential candidates for a possible topical treatment of HSV infections.…”

“…Naturally occuring humic acids were found to be highly active against HSV (Klöcking & Sprössig, 1975;Thiel et al, 1977). Synthetic humic acid-like polymers, the so-called polyhydroxycarboxylates, produced from phenolic starting compounds, were shown to inhibit the replication of HSV (Thiel et al, 1976Klöcking et al, 1983;Neyts et al, 1992b), HCMV (Neyts et al, 1992b) and HIV (Schols et al, 1991). We have now selected various newly synthesized compounds of this type and have studied their potential antiviral activity against several herpesviruses and HIV.…”

Anti-Herpes Simplex Virus Type 1 Activity of Humic Acid-Like Polymers and Their O-Diphenolic Starting Compounds

“…In particular, it was suggested by Schols et al (1991) for human immunodeficiency virus and by Neyts et al (1992) for human cytomegalovirus that poly(hydroxy) carboxylates exhibit their antiviral effects by interaction with positively charged domains ofviral envelope glycoproteins. Therefore, the antiviral activity of poly(hydroxy)carboxylates depends on the number of negatively charged functional groups per molecule (Schols et al, 1991).…”

“…Synthetic HA-like polymers, also called poly(hydroxy)carboxylates, which are produced from phenolic starting compounds, are also inhibitory to HSV (Thiel et al, 1976Neyts et al, 1992).…”