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

被引:12
作者
Di Caro, A
Perola, E
Bartolini, B
Marzano, M
Liverani, L
Mascellani, G
Benedetto, A
Cellai, L
机构
[1] CNR, Ist Strutturist Chim G Giacomello, I-00016 Monterotondo, Roma, Italy
[2] IRCCS L Spallanzani, Ctr Virol, I-00149 Rome, Italy
[3] OPOCRIN, I-41040 Modena, Italy
关键词
oversulphated chondroitins; oversulphated dermatans; HIV; HSV; HCMV; AIDS;
D O I
10.1177/095632029901000104
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of chemically oversulphated galactosaminoglycans (SO3H:COOH ratio greater than or equal to 2) were tested in vitro as antiviral agents against human immunodeficiency virus type 1 (HIV-1), the aetiological 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. I). 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-l compound (EC50 0.04 mu g/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 mu g/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 mu g/ml). In view of the absence of the side-effects typical of heparin-like compounds, a combination of these derivatives could have therapeutic potential.
引用
收藏
页码:33 / 38
页数:6
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