In Vitro Three Categories As Candidate Microbicides Against HIV-1_IIIB Activities And Antiviral Mechanism

AIDS is the most serious disease for human health.During the struggle against AIDS,people revealed out the pathogen of AIDS,developed many antiviral drugs,which reduced the incidence of AIDS and mortality rate,but AIDS is not cured yet.At present,sexual transmission plays a major role in the spread of HIV in the world.More than 90%of new HIV infections are spreading through unprotected intercourse in whole world.The relentlessness of the HIV/AIDS epidemic and its growing feminization have prompted people to acknowledge the urgency to develop new prevention technologies. Microbicides are now recognized as among the most promising prevention technologies on the horizon.To develop a microbicide used under women control has been recognized as an important method as vaccine of HIV to control transmission of HIV-1.There has been significant progress in microbicide research and development in the past 15 years.Over 30 compounds or formulations are undergoing preclinical or clinical studies. However,the number of potential products is not large enough.Discovery of novel compounds for use as potential microbicide candidates is a long-term task.In this paper,we focused on the developing novel microbicides from traditional Chinese medicine,lectins and rare earth elements.The IC₅₀values of sulfated polysaccharide D2,D3,D6,D8,D9 were (10.28±1.12)μg/ml,(10.90±1.08)μg/ml,(8.72±1.08)μg/ml,(15.10±1.08)μg/ml, (11.10±1.09)μg/ml,and the SI values were 261,331,313,213,203, respectively.The rare earth element CCYCN had anti-HIV-1_â…¢Bactivity,its IC₅₀value was(4.02±1.07)μg/ml,and its selective index(SI)value was 229. The unsulfated polysaccharide compounds DN,DN1,DN2,which were obtained by different methods,also could inhibit HIV-1_â…¢Bactivity,their IC₅₀values were(33.12±1.08)μg/ml,(27.19±1.08)μg/ml,(10.68±1.08)μg/ml, their selective indexs(SIs)values were 22,28,87,respectively.According to anti-HIV-1_â…¢Bactivity experiment,we knew the sulfated polysaccharide compounds D2,D3,D6,D8,D9 had better anti-HIV-1_â…¢B activities than other compounds.In order to know the antiviral mechanisms of the compounds D2,D3,D6,D8,D9,time-addition assay,fusion and different pre-treatments were used.The results showed that the sulfated polysaccharide D2,D3,D6,D8,D9 may affect the early stage of HIV life cycle.We also studied on the stabilities of the sulfated polysaccharide compounds D3 and D6.SPSS15.0 was used to analyze data we acquired,the results showed the IC₅₀values of D3 and D6 had the notable relation of linearity.In a word,the sulfated polysaccharide compounds D3 and D6 demonstrated strong anti-HIV-1_â…¢Bactivities,and may be potential candidates for microbicides development.They shoud be further studied on antiviral mechanism and stability in the future.