Viral surface glycoproteins, gp120 and gp41, as potential drug targets against HIV-1: Brief overview one quarter of a century past the approval of zidovudine, the first anti-retroviral drug

HIV-1 Glycoprotein Immunogenicity

“…This pattern is surrounded by variable amino acids which alter the viral tropism through interaction of gp120 with the cellular chemokine CCR5 and CXCR4. The V1-V5 regions form exposed loops anchored at their bases by disulfide bonds (Teixeira et al, 2011). Crystal structure of gp120 shows that this protein is folded as a connection of four elements called "bridging sheet"with an inner and an outer domain (Kwong et al, 1998).…”

“…Crystallographic and biochemical studies of gp120 have provided valuable insights into mechanisms involved in CD4-binding and CD4-induced conformational changes that result in formation and exposure of the co-receptor binding site (Huang et al, 2005;Myszka et al, 2000). The unbound gp120 core consists of a highly conserved inner domain, which faces the trimer axis, and a heavily glycosylated, outer domain, which is mostly exposed on the surface of the trimmer (Kwong et al, 1998;Teixeira et al, 2011;Zolla-Pazner and Cardozo, 2010). CD4 binding site represents the encounter of three separate regions via their surface-exposed residues.…”

The State of the Science: A 5 - Year Review on the Computer - Aided Design for Global Anti - AIDS Drug Development

“…On the other hand, gp120 is also divided into three functional regions, an inner domain involved in interactions with gp41 and the formation of trimer that is the bioactive conformation of gp120, an outer domain exposed to the molecule surface and is highly glycosylated, and a bridging sheet resulted by the great conformational change following the binding of CD4 and gp120 (Teixeira et al, 2011). Multi-target HIV-1 entry inhibitors hexa-arginine-neomycin-conjugate (NeoR6) and nona-Darginine-neomycin-conjugate (Neo-r9) are mimics of V3 loop of gp120 which is involved in the interaction between HIV-1 and CXCR4, exhibiting high antiviral potent and low cytotoxicity.…”

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

“…Approximately 40% of the AZT dose is metabolized presystemically (Carvalho et al, 2009;Teixeira et al, 2011). Due to its low bioavailability, oral administration of AZT poses a major challenge to the development of new systems for controlled drug release.…”