SAR studies of aminoglycoside-arginine peptidomimetics targeting HIV-1 entry step

摘要

For human immunodeficiency virus type 1(HIV-1)to enter a cell,its envelope-protein(Env)must sequentially engage CD4 and a chemokine coreceptor,triggering conformational changes in Env that ultimately lead to fusion between the viral and host cell membranes.Each step of the virus entry pathway is a potential target for novel antiviral agents termed entry inhibitors.The envelope is composed of two subunits,glycoprotein 120(gpl20)and glycoprotein 41(gp41).The discovery of virus entry mechanisms and consequent understanding the receptor-induced conformational changes in the Env and virus-cell fusion,led to the development of entry inhibitors,The overall viral entry process(binding and fusion)can be blocked by a number of compounds.One of these entry inhibitors,T20,has been approved for clinical use.Because all entry inhibitors target the viral Env directly or indirectly and Env is the most variable of the HIV-1 proteins,primary viruses differ significantly in their sensitivity to entry inhibitors.The actual viral factors that influence entry-inhibitors involve variations in gpl20 and gp41.