Screening of Compounds for Activity against HIV: A Collaborative Study

Author:

Holmes H. C.1,Mahmood N.2,Karpas A.3,Petrik J.3,Kinchington D.4,O'Connor T.4,Jeffries D. J.4,Desmyter J.5,De Clercq E.5,Pauwels R.5,Hay A.6

Affiliation:

1. WHO Collaborating Centre for AIDS, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, UK

2. MRC Collaborative Centre, Burtonhole Lane, Mill Hill, London NW7 1AD, UK

3. Department of Haematology, Clinical School, University of Cambridge, Hills Road, Cambridge CB2 2QL, UK

4. Department of Virology, Medical College of St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK

5. Rega Institute for Medical Research, Katholieke Universität Leuven, Minderbroederstraat 10, B-3000 Leuven, Belgium

6. National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

Abstract

The collaborative study was undertaken to examine the sensitivity of a range of tests used in assessing the antiviral activities of compounds against human immunodeficiency virus (HIV). A panel of 20 compounds with diverse antiviral activities against HIV were tested under code at three antiviral testing centres supported by the Medical Research Council's AIDS Directed Programme and at the European Community Centralised Facility (ECCF) for New Antiviral Compounds against AIDS in Belgium. Compounds known to have major anti-HIV activity ranked high in all assays, with the exception of the glucosidase inhibitors and certain nucleoside analogues. Results of two assays based on MT4 cells (centre IV) showed a high degree of similarity, despite the use of distinct HIV-1 (HTLV-IIIB) and HIV-2 (ROD) viruses. Considerable similarity was also observed between the assays based on HTLV-IIIRF in C8166 cells (centres I and II). Other assays performed at centre II and at centre III had enhanced sensitivity for glycosidase inhibitors. The differences in anti-HIV activity that were observed may be attributable to specific properties of the cell lines used and particular testing methodologies. The use of more than one type of assay is advisable in order not to miss compounds with low to moderate activity against HIV.

Publisher

SAGE Publications

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