HIV-1 Membrane Fusion

Doms, Robert W.; Moore, John P.

doi:10.1083/jcb.151.2.f9

Cited by 258 publications

(85 citation statements)

References 23 publications

(40 reference statements)

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“…The process of HIV-1 entry into target cells is an attractive target for antiviral intervention (5)(6)(7). Inhibitors that target this stage of the viral life cycle are highly unlikely to share crossresistance with the existing protease and reverse transcriptase inhibitors, which interfere with later events in viral replication.…”

mentioning

confidence: 99%

“…or s.c. to HIV-1-infected individuals (9,10). Other entry inhibitors are also in preclinical or early clinical development (5)(6)(7)11).…”

mentioning

confidence: 99%

“…Inhibitors that target this stage of the viral life cycle are highly unlikely to share crossresistance with the existing protease and reverse transcriptase inhibitors, which interfere with later events in viral replication. The receptor-mediated events that drive membrane fusion are increasingly well understood from a molecular perspective, and several individual stages have been identified as being susceptible to pharmacological intervention (7). The potential for entry inhibitors to be useful drugs has been established by the T-20 peptide, which blocks the conformational changes in HIV-1 gp41 that are necessary for virus-cell fusion (8).…”

mentioning

confidence: 99%

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SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infectionin vitroandin vivo

Strizki

Wagner

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy͞Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50 -60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.

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mentioning

confidence: 99%

“…or s.c. to HIV-1-infected individuals (9,10). Other entry inhibitors are also in preclinical or early clinical development (5)(6)(7)11).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infectionin vitroandin vivo

Strizki

Wagner

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

297

186

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“…The tissue and cellular tropisms of viruses are often regulated by one or more host receptors that mediate distinct functions such as viral attachment, internalization, fusion, and trafficking (2,3). CD81 and the low-density lipoprotein receptor (LDL-R) have been identified as putative attachment and entry receptors for HCV (4,5).…”

mentioning

confidence: 99%

L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus

Gardner

Durso

Arrigale

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

262

221

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“…[1][2][3][4] A current model of such an entry process involves the initial binding of gp120 to the primary cell surface receptor CD4 and chemokine coreceptor CXCR4 or CCR5. 5,6 Following receptor-binding events and the subsequent attendant conformational changes, the dissociation of gp120 from gp41 results in…”

Section: Introductionmentioning

confidence: 99%

Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV fusion‐active intermediate state

Sadler

Zhang

et al. 2008

Biopolymers

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During viral entry, the fusogenic state of human immunodeficiency virus Type 1 (HIV‐1) envelope protein gp41 is a quaternary structure consisting of three gp41 glycoproteins, each with two conserved helical domains (N‐HR and C‐HR). Thus far, the examination of monomeric gp41 peptides as an immunologically focused approach to vaccine design has not been successful. Here we report an approach using quaternary protein mimetics (called 3α mimetics) that are based on the gp41 N‐HR and C‐HR domains to closely mimic the fusogenic state and overcome the deficiencies of the monomeric peptide approach for synthetic vaccine design. The 3α mimetics are conveniently prepared by chemoselective ligation of unprotected monomeric peptides to an interstrand linker, and display enhanced conformational stability compared to the corresponding monomers. The 3α mimetics with or without a covalently attached T‐helper epitope were immunogenic and elicited antisera that bound both recombinant gp160, which contains gp41, and HIV‐1 virions and immunoprecipitated recombinant gp41. Anti‐3α mimetic antisera neutralized viral infectivity against R5‐ and X4‐tropic strains of HIV‐1 at 31.5°C. The results suggest that a quaternary protein approach to mimic conserved and functional domains of viral envelope proteins is desirable for HIV vaccine development as such antigens are more likely to produce immunologically‐focused and broadly neutralizing antibody responses. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 320–329, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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HIV-1 Membrane Fusion

Cited by 258 publications

References 23 publications

SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infectionin vitroandin vivo

SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infectionin vitroandin vivo

L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus

Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV fusion‐active intermediate state

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