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Abstract
THE TRIPEPTIDES GPG-NH2 AND ALG-NH2 INTERFERE WITH HIV-1 BUDDING AND CAPSID ASSEMBLY: A NEW STRATEGY FOR ANTIVIRAL THERAPY
VAHLNE A, SU J, HÖGLUND S, SANDIN RENEBY S, GOOBAR-LARSSON L, NYSTRÖM I, VÉGVÁRI A
The assembly of virus capsids is a potential target for antiviral therapy. The Gag polyprotein of HIV-1 particles contains the sequence for the matrix (p19, MA), the capsid (p24, CA), nucleocapsid (p7, NC) and p6 proteins and two spacer peptides (SP1) and (SP2). Here, we report that seven of 83 tripeptide amides from the carboxyl terminal sequence of p24 suppressed HIV-1 replication. The two most potent tripeptides, GPG-NH2 and ALG-NH2, were found to interact with p24. HIV-1 particles from GPG-NH2 and ALG-NH2 treated cells had disarranged capsid structures as observed in electron microscopy (TEM and 3D computor model reconstructions from tilt series TEM). Furthermore, nodular structures having the size of the broad end of HIV-1 capsids were observed at the plasma membranes of treated cells only, indicating an arrest of the budding process. Corresponding non-amidated tripeptides did not interact with p4 and were not biologically active. Treatment with tripeptide amides interfering with virus capsid assembly represents a new startegy for antiviral therapy. GPG-NH2 is efficiently adsorbed from the gut by the pept1/pept2 oligopeptide transport system, as observed in both in vitro (Caco-2 cells) and in vivo (experimental anials and man). GPG-NH2 has also been shown to decrease viral loads in a small phase I/II clinical study and is presently undergoing a phase II clinical study at ten different centers in Europe.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
119
Suggested Citation
"VAHLNEA, et al.
THE TRIPEPTIDES GPG-NH2 AND ALG-NH2 INTERFERE WITH HIV-1 BUDDING AND CAPSID ASSEMBLY: A NEW STRATEGY FOR ANTIVIRAL THERAPY.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
119"
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