Fractions of Chemically Oversulphated Galactosaminoglycan Sulphates Inhibit Three Enveloped Viruses: Human Immunodeficiency Virus Type 1, Herpes Simplex Virus Type 1 and Human Cytomegalovirus

Abstract

A series of chemically oversulphated galactosaminoglycans (SO₃H:COOH ratio ≥2) were tested in vitro as antiviral agents against human immunodeficiency virus type 1 (HIV-1), the aetio-logical agent of AIDS, and against herpes simplex virus type 1 and human cytomegalovirus, two agents responsible for opportunistic infections in HIV-infected people. The oversulphated derivatives displayed an increase in activity ranging from one to four orders of magnitude against the three viruses, as compared to the natural parent compounds (SO₃H:COOH, ratio approx. 1). The antiviral activity of these polyanions appears to be favoured by a high degree of sulphation and a high molecular mass. An oversulphated dermatan, with a SO₃H:COOH ratio of 2.86 and molecular mass of 23.2 kDa, was the most potent anti-HIV-1 compound (EC₅₀ 0.04 µg/ml). A second oversulphated dermatan, with a SO₃H:COOH ratio of 2.40 and molecular mass of 25 kDa, displayed the highest activity against HSV-1 (EC₅₀ 0.01 µg/ml). An oversulphated chondroitin, with a SO₃H:COOH ratio of 2.80 and molecular mass of 17.3 kDa, was the strongest anti-HCMV agent (EC₅₀ 0.4 µg/ml). In view of the absence of the side-effects typical of heparin-like compounds, a combination of these derivatives could have therapeutic potential.