Fractions of chemically oversulphated galactosaminoglycan sulphates inhibit three enveloped viruses: human immunodeficiency virus type 1, herpes simplex virus type 1 and human cytomegalovirus

A series of chemically oversulphated galactosaminoglycans (SO3H:COOH ratio greater than or equal to 2) were tested in vitro as antiviral agents agains t human immunodeficiency virus type 1 (HIV-1), the aetiological agent of AI DS, 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 o ne to four orders of magnitude against the three viruses, as compared to th e natural parent compounds (SO3H:COOH, ratio approx. I). The antiviral acti vity of these polyanions appears to be favoured by a high degree of sulphat ion 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- l compound (EC50 0.04 mu g/ml). A second oversulphated dermatan, with a SO3 H:COOH ratio of 2.40 and molecular mass of 25 kDa, displayed the highest ac tivity against HSV-1 (EC50 0.01 mu g/ml). An oversulphated chondroitin, wit h a SO3H:COOH ratio of 2.80 and molecular mass of 17.3 kDa, was the stronge st anti-HCMV agent (EC50 0.4 mu g/ml). In view of the absence of the side-e ffects typical of heparin-like compounds, a combination of these derivative s could have therapeutic potential.