didanosine and miglustat

Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs.

Topics: 1-Deoxynojirimycin; Algorithms; Anti-HIV Agents; CCR5 Receptor Antagonists; Computer Simulation; Cyclohexanes; Databases, Chemical; Didanosine; Drug Design; Drug Discovery; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Maraviroc; Models, Molecular; Protein Interaction Mapping; Protein Interaction Maps; Receptors, CCR5; Triazoles

The effects on HIV-1 infection of a glucosidase inhibitor, N-butyl deoxynojirimycin (N-buDNJ), were examined. The combinations of N-buDNJ and nucleoside analogs dideoxyinosine (DDI), dideoxycytidine (DDC), or azidothymidine (AZT) were examined in an acute infection assay. The combination of N-buDNJ and nucleoside analog reduced the yield of reverse transcriptase activity more than did either agent alone, and the effects on the number of infectious virus particles were additive or synergistic. In studies of the mechanism whereby N-buDNJ alters HIV-1 envelope fusion activity, no effects on CD4 binding were detected. However, cleavage within the V3 loop of gp120 was reduced by N-buDNJ treatment, possibly reflecting an altered conformation of this region of the envelope protein.

Topics: 1-Deoxynojirimycin; Antiviral Agents; CD4 Antigens; Cell Line; Didanosine; Drug Interactions; HIV Envelope Protein gp120; HIV-1; Humans; Nucleosides; Zalcitabine; Zidovudine