Objective
Although intensive effort has been made to understand the genetic and immunological aspects of infection by retroviruses, little is known about the molecular mechanism of fusion of the HIV viral envelope with the host cell plasma membrane.
The main objective of the Concerted Action (Rational design of antiviral agents inhibiting the fusogenic activity of HIV) of Dr. RUYSSCHAERT group (in collaboration with Dr. V. ERFLE, Germany and Dr. T. SAERMARK, Denmark) is to identify components involved in this fusion process and to synthesize, on a rational basis, agents interacting specifically with these targets, in order to block the fusion and therefore HIV viral infection. They provided evidence that drug inhibiting either the insertion of the N-terminal domain of HIV gp41 or the inverted micelles formation completely abolished the HIV fusogenic activity and consequently the viral infectivity (I. Martin, M.c. Dubois, T. Saermark, R.M. Epand and J.-M. Ruysschaert, FEBS Letters 333, 325-330, 1993; I. Martin, M.C. Dubois, F. Defrise-Quertain, T. Saermark, A. Burny, R. Brasseur and J.-M. Ruysschaert, J. Virology 68, 2, 1139-1148, 1994). Other putative targets have been suggested and one of them is the V3 loop on gp120. Prof. B. PENKE and prof. J. MOLNAR (Hungary) major objective will be to build peptides complementary (in terms of amino acid charges, amino acid volumes, hydrogen bond formation, hydrophobic interaction) to sequences of V3, a loop associated to gp120 which has been shown to be implicated in the host cell-virus fusion. This interaction will be modelized using molecular dynamics calculations (Z. Szekely, A. Perczel, B. Penke and J. Molnár J. Mol. Struct. 286, 165-182, 1993). The most interactive peptides will be synthesized and purified in prof. B. PENKE laboratory Their antifusogenic activity will be tested on model membranes in Dr. RUYSSCHAERT team and their antiviral activity will be examined in Dr. V. ERFLE laboratory (Germany).
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Programme(s)
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Topic(s)
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1050 BRUXELLES
Belgium
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.