Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More and more women are becoming infected with HIV. While the use of male condoms greatly reduces the transmission of HIV, the condoms must be used correctly and consistently in order to confer protection against contracting an infection, and their use is not controlled by women. Female condoms are a barrier method which women can use, but there use may be objectionable to some men, who can see the condoms' outer ring. However, women can easily control the use of vaginal microbicides. Several such products are being researched. Some use nonoxynol-9 or other surfactants, while others include acid buffering gels; natural products such as lactobacillus crispatus, antimicrobial peptides, magainins, or plant extracts; inhibitors of viral entry; post-binding fusion inhibitors; and reverse transcriptase inhibitors. While in vitro tests have found that spermicides containing nonoxynol-9 (N-9) kill organisms which cause gonorrhea, genital herpes, trichomoniasis, syphilis, and AIDS, the disruptive effect of N-9 upon the vaginal epithelium raises questions upon the merit of their use and their overall effectiveness in preventing disease transmission. The ideal microbicide should be effective against HIV/STDs, nonirritating, long-acting, inexpensive, readily available, and easy to use. It should be available in spermicidal and nonspermicidal formulations.
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PMID:Vaginal microbicides needed for female-controlled prevention. 1232 62

A structurally novel candidate microbicide, PPCM, which is formed from the reaction of D,L-mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant cultures, explore the possibility of combining PPCM with HIV-specific reverse transcriptase inhibitors, and evaluate the efficacy of a formulated gel against genital herpes in a murine model. PPCM inhibited infection by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical and endocervical tissue explants exposed to HIV-1(BaL) in the presence of PPCM were protected (50% inhibitory concentrations [IC(50)] of 3.9 microg/ml for ectocervix and 3.1 microg/ml for endocervix), and transfer of virus to target T cells via migratory cells was significantly impaired (IC(50) of 35.7 microg/ml for ectocervix and 54.6 microg/ml for endocervix). The drug also blocked infection by cell-associated virus. Combinations of PPCM with UC-781 or PMPA in vitro exhibited additive anti-HIV activity. PPCM was incorporated into stable, low-pH gel formulations at concentrations of 0.4% and 4%. Both gels prevented genital herpesvirus infection in mice, even when virus was introduced in human seminal plasma. The abilities of PPCM to inhibit primary HIV isolates, reduce infection by cell-associated virus, and transfer of HIV from migratory to T cells, combined with the complete protection provided by formulated gel against genital herpes, indicate that this drug is an excellent candidate for inclusion in a combination microbicide and would provide protection against both HIV and HSV.
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PMID:Candidate microbicide PPCM blocks human immunodeficiency virus type 1 infection in cell and tissue cultures and prevents genital herpes in a murine model. 1843 7