PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-4 (4)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
Document Types
1.  The Role of Dynamin in HIV Type 1 Env-Mediated Cell–Cell Fusion 
AIDS Research and Human Retroviruses  2011;27(9):1013-1017.
Abstract
HIV-1 envelope glycoproteins are the key viral proteins that mediate HIV-1 entry and cell–cell fusion. In contrast to HIV-1 entry, the mechanism of HIV-1 Env-mediated cell–cell fusion is relatively unclear. This study demonstrated that dynasore, a dynamin inhibitor, suppressed HIV-1 Env-mediated cell–cell fusion. Dynasore sensitivity of HIV-1 Env-mediated cell–cell fusion varied depending on the viral strains. Results from testing a panel of gp41 cytoplasmic tail truncation mutants suggested that the gp41 cytoplasmic tail might play a role in dynasore sensitivity. HIV-1 Env-mediated cell–cell fusion could also be suppressed by a dynamin dominant-negative mutant DNM2(K44A). In summary, these results suggested that dynamin 2 might play a role in HIV-1 Env-mediated cell–cell fusion.
doi:10.1089/aid.2010.0259
PMCID: PMC3161105  PMID: 21338326
2.  Betulinic Acid Derivatives as Human Immunodeficiency Virus Type 2 (HIV-2) Inhibitors 
Journal of medicinal chemistry  2009;52(23):7887-7891.
We previously reported that [[N-[3β-hydroxyl-lup-20(29)-en-28-oyl]-7-aminoheptyl]-carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betulinic acid derivatives were synthesized, and some of them displayed selective anti-HIV-2 activity at nanomolar concentrations. In comparison to compounds with anti-HIV-1 activity, a shorter C-28 side chain is required for optimal anti-HIV-2 activity.
doi:10.1021/jm9004253
PMCID: PMC2788670  PMID: 19526990
Betulinic acid; HIV-2; HIV-1
3.  Discovery of diarylpyridine derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors 
Two series (4 and 5) of diarylpyridine derivatives were designed, synthesized, and evaluated for anti-HIV-1 activity. The most promising compound, 5e, inhibited HIV-1 IIIB, NL4-3, and RTMDR1 with low nanomolar EC50 values and selectivity indexes of >10,000. The results of this study indicate that diarylpyridine can be used as a novel scaffold to derive a new class of potent NNRTIs, active against both wild-type and drug resistant HIV-1 strains.
doi:10.1016/j.bmcl.2009.07.080
PMCID: PMC2770631  PMID: 19666220
diarylpyridine derivatives; HIV-1 NNRTIs; drug resistance
4.  Betulinic Acid Derivatives That Target gp120 and Inhibit Multiple Genetic Subtypes of Human Immunodeficiency Virus Type 1▿  
Betulinic acid (BA) derivatives can inhibit human immunodeficiency virus type 1 (HIV-1) entry or maturation depending on side chain modifications. While BA derivatives with antimaturation activity have attracted considerable interest, the anti-HIV-1 profile and molecular mechanism of BA derivatives with anti-HIV-1 entry activity (termed BA entry inhibitors) have not been well defined. In this study, we have found that two BA entry inhibitors, IC9564 and A43D, exhibited a broad spectrum of anti-HIV-1 activity. Both compounds inhibited multiple strains of HIV-1 from clades A, B, and C at submicromolar concentrations. Clade C viruses were more sensitive to the compounds than clade A and B viruses. Interestingly, IC9564 at subinhibitory concentrations could alter the antifusion activities of other entry inhibitors. IC9564 was especially potent in increasing the sensitivity of HIV-1YU2 Env-mediated membrane fusion to the CCR5 inhibitor TAK-779. Results from this study suggest that the V3 loop of gp120 is a critical determinant for the anti-HIV-1 activity of IC9564. IC9564 escape viruses contained mutations near the tip of the V3 loop. Moreover, IC9564 could compete with the binding of V3 monoclonal antibodies 447-52D and 39F. IC9564 also competed with the binding of gp120/CD4 complexes to chemokine receptors. In summary, these results suggest that BA entry inhibitors can potently inhibit a broad spectrum of primary HIV-1 isolates by targeting the V3 loop of gp120.
doi:10.1128/AAC.00737-07
PMCID: PMC2223896  PMID: 17954689

Results 1-4 (4)