Meta-Engineering In Drug Design: A Roadmap To Implement A Novel Liposome-Based Testbed

Retroviruses cause a variety of the most serious diseases of man and animals. A new class of antiretroviral drugs, so-called 'entry inhibitors', block virus entry into the host cell. Until now, antiretroviral drug have been designed and evaluated in complex natural virus-cell systems, but the complexity impedes detailed insights into the underlying molecular mechanisms of virus-cell interaction. Therefore, we propose to engineer a novel model system which reduces the complexity of the components involved in virus-cell interaction. The proposed artificial model system will provide an in vitro testbed for antiretroviral drug design and validation. The system will combine the advantages of natural and artificial models by consisting of artificial lipo-somes equipped with a minimal cellular machinery providing nothing but the components needed for the molecular processes in virus-cell interaction. We are able to refer to data of several 'entry inhibitors' tested in a natural virus-cell system, and we already established liposome containers separated from the surrounding by a lipid membrane that enclose sugars, and amino acids. Here, we present results of encapsulating nucleotides and organic and inorganic ions. Further, we discuss how to proceed on the way towards a novel liposome-based testbed for antiretroviral drug design and validation.