HIV-1 cell entry and advances in viral entry inhibitor therapy

Cooley, Louise; Lewin, Sharon R.

doi:10.1016/s1386-6532(02)00111-7

Cited by 56 publications

(44 citation statements)

References 41 publications

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“…ne of the most critical events in the HIV infection process is entry of human immunodeficiency virus type 1 (HIV-1) into target cells; this is, therefore, considered an important target for developing antiviral drugs (1)(2)(3). Already, approval of two HIV-1 entry inhibitor drugs, enfuvirtide (Fuzeone; T-20) (4) and maraviroc (Selzentry) (5,6), has validated entry prevention as a successful strategy in antiviral drug design.…”

mentioning

confidence: 99%

Binding Mode Characterization of NBD Series CD4-Mimetic HIV-1 Entry Inhibitors by X-Ray Structure and Resistance Study

Curreli

Kwon

Zhang

et al. 2014

Antimicrob Agents Chemother

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We previously identified two small-molecule CD4 mimetics-NBD-556 and NBD-557-and synthesized a series of NBD compounds that resulted in improved neutralization activity in a single-cycle HIV-1 infectivity assay. For the current investigation, we selected several of the most active compounds and assessed their antiviral activity on a panel of 53 reference HIV-1 Env pseudoviruses representing diverse clades of clinical isolates. The selected compounds inhibited tested clades with low-micromolar potencies. Mechanism studies indicated that they act as CD4 agonists, a potentially unfavorable therapeutic trait, in that they can bind to the gp120 envelope glycoprotein and initiate a similar physiological response as CD4. However, one of the compounds, NBD-09027, exhibited reduced agonist properties, in both functional and biophysical studies. To understand the binding mode of these inhibitors, we first generated HIV-1-resistant mutants, assessed their behavior with NBD compounds, and determined the X-ray structures of two inhibitors, NBD-09027 and NBD-10007, in complex with the HIV-1 gp120 core at ϳ2-Å resolution. Both studies confirmed that the NBD compounds bind similarly to NBD-556 and NBD-557 by inserting their hydrophobic groups into the Phe43 cavity of gp120. The basic nitrogen of the piperidine ring is located in close proximity to D368 of gp120 but it does not form any H-bond or salt bridge, a likely explanation for their nonoptimal antagonist properties. The results reveal the structural and biological character of the NBD series of CD4 mimetics and identify ways to reduce their agonist properties and convert them to antagonists.

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confidence: 99%

Binding Mode Characterization of NBD Series CD4-Mimetic HIV-1 Entry Inhibitors by X-Ray Structure and Resistance Study

Curreli

Kwon

Zhang

et al. 2014

Antimicrob Agents Chemother

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“…With up to 20% of the new infections involving variants resistant to current medications, antiretroviral agents targeting new steps in the replicative cycle and lacking crossresistance to existing drug classes are urgently needed for managing HIV infection (24,44). The recent introduction of a novel fusion inhibitor and other potential entry inhibitors will likely provide an expanded range of treatment options for anti-HIV therapy (7,20,29,31).…”

mentioning

confidence: 99%

“…The potential intervention steps in the entry process (and their respective inhibitors) are gp120-CD4 binding (BMS-488043, PRO-542), gp120-coreceptor interactions (SCH D, UK-427857, GW-873140), and gp41-induced membrane fusion (Enfuvirtide). These inhibitors have exhibited clinical efficacy in HIV-infected patients (7,12,20,26).…”

mentioning

confidence: 99%

Envelope Conformational Changes Induced by Human Immunodeficiency Virus Type 1 Attachment Inhibitors Prevent CD4 Binding and Downstream Entry Events

Ho¹,

Fan²,

Nowicka-Sans³

et al. 2006

J Virol

102

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“…However, the emergence of drug resistance has been observed 3,4 , therefore, new therapeutic agents are still needed. Recently, a new class of therapeutic agents has focused on inhibiting HIV entry into cells, CD4 binding, co-receptor binding and membrane fusion such as T-20 5 .…”

Section: Introductionmentioning

confidence: 99%

Untitled

2011

IJPSR

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In present QSAR study of TIBO derivatives, aim of the author is to analysis some different 3D parameter in order to get best QSAR model, which enhance the binding affinity of TIBO derivatives. Solvent accessible surface area (3D) of all atoms with positive partial charge (strictly greater than 0) and Balaben 3D index plays vital role in this concern. This study focuses on some important and different 3D parameter in place of other conventional 3D parameter. The greater value of multiple R (= 0.9421) and lower value of Standard error (Se= 0.4981) shows that the find mathematical model is best fit and give the structural requirements of TIBO derivatives in particular sets of compounds to enhance the binding affinity of the drug.

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HIV-1 cell entry and advances in viral entry inhibitor therapy

Cited by 56 publications

References 41 publications

Binding Mode Characterization of NBD Series CD4-Mimetic HIV-1 Entry Inhibitors by X-Ray Structure and Resistance Study

Binding Mode Characterization of NBD Series CD4-Mimetic HIV-1 Entry Inhibitors by X-Ray Structure and Resistance Study

Envelope Conformational Changes Induced by Human Immunodeficiency Virus Type 1 Attachment Inhibitors Prevent CD4 Binding and Downstream Entry Events

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