Natural HIV-1 protease (PR) is homodimeric. Some researchers believe that interactions between HIV-1 Gag-Pol molecules trigger the activation of embedded PR (which mediates Gag and Gag-Pol cleavage), and that Gag-Pol assembly domains outside of PR may contribute to PR activation by influencing PR dimer interaction in a Gag-Pol context. To determine if the enhancement of PR dimer interaction fac...

Laboratory-adapted (LA) macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1) isolates (e.g., HIV-1(Ba-L)) and low-passage primary (PR) isolates differed markedly in tropism for syngeneic neonatal monocytes, monocyte-derived macrophages (MDMs), and placental macrophages (PMs). Newly adherent neonatal monocytes and cultured PMs were highly refractory to infection with PR HIV-1...

The protease (PR) of Murine leukemia virus (MLV) was expressed in Escherichia coli, purified to homogeneity and characterized by using various assay methods, including HPLC-based, photometric and fluorometric activity measurements. The specificity of the bacterially expressed PR was similar to that of virion-extracted PR. Compared with human immunodeficiency virus type 1 (HIV-1) PR, the pH opti...

Novel antiretroviral drugs include protease (PR) inhibitors (e.g. atazanavir, tipranavir and darunavir) that block HIV-1 maturation and show remarkable antiviral potency on drug-resistant isolates. However, the strains used as prototypes in the design of the novel drugs belong to a specific clade (i.e. HIV-1 group M subtype B), which is the most prevalent in developed countries. At the same tim...

The kinetic properties of two classical inhibitors of aspartic proteases (PRs), pepstatin A and acetyl-pepstatin, were compared in their interactions with HIV-1 and xenotropic murine leukemia virus related virus (XMRV) PRs. Both compounds are substantially weaker inhibitors of XMRV PR than of HIV-1 PR. Previous kinetic and structural studies characterized HIV-1 PR-acetyl-pepstatin and XMRV PR-p...

Soon after its discovery, the attempts to develop anti-AIDS therapeutics focused on the retroviral protease (PR)-an enzyme used by lentiviruses to process the precursor polypeptide into mature viral proteins. An urgent need for the three-dimensional structure of PR to guide rational drug design prompted efforts to produce milligram quantities of this enzyme. However, only minute amounts of PR w...

The drug Darunavir (DRV) is a potent inhibitor of HIV-1 protease (PR), a homodimeric essential enzyme of the AIDS virus. Recent experimental data suggest that DRV is able to prevent dimerization of HIV-1 PR, which, together with its high affinity for the mature enzyme, has been linked to the high genetic barrier to the development of viral resistance. The mechanism of dimerization inhibition an...

The human immunodeficiency virus protease (HIV-1 PR) was expressed both in the yeast Saccharomyces cerevisiae and in mammalian cells. Inducible expression of HIV-1 PR arrested yeast growth, which was followed by cell lysis. The lytic phenotype included loss of plasma membrane integrity and cell wall breakage leading to the release of cell content to the medium. Given that neither poliovirus 2A ...

Dimerization of HIV-1 protease (PR) subunits is an essential process for PR's acquisition of proteolytic activity, which plays a critical role in the maturation of HIV-1. Recombinant wild-type PR (PR(WT)) proved to dimerize, as examined with electrospray ionization mass spectrometry; however, two active site interface PR mutants (PR(T26A) and PR(R87K)) remained monomeric. On the other hand, two...

A fundamental issue related to therapy of HIV-1 infection is the emergence of viral mutations which severely limits the long term efficiency of the HIV-protease (HIV-PR) inhibitors. Development of new drugs is therefore continuously needed. Chemoinformatics enables to design and discover novel molecules analogous to established drugs using computational tools and databases. Saquinavir, an anti-...