http://stm.sciencemag.org/content/2/63/63re3.abstract?sid=1ff8a49f-5b09-4a71-9e62-8d2a99459a6eSci Transl Med 22 December 2010:
Vol. 2, Issue 63, p. 63re3
DOI: 10.1126/scitranslmed.3001697
Reports
Short-Term Monotherapy in HIV-Infected Patients with a Virus Entry Inhibitor Against the gp41 Fusion Peptide
Wolf-Georg Forssmann1,2,3, Yu-Han The1, Matthias Stoll1, Knut Adermann1,2,3, Uwe Albrecht4, Kleomenis Barlos5,6, Annette Busmann1,2, Angeles Canales-Mayordomo7, Guillermo Giménez-Gallego7, Jochen Hirsch1,2,3, Jesus Jiménez-Barbero7, Dirk Meyer-Olson1, Jan Münch8, Javier Pérez-Castells9, Ludger Ständker1, Frank Kirchhoff8,* and Reinhold E. Schmidt1
1Department of Immunology and Rheumatology, Hannover Medical University, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
2VIRO Pharmaceuticals GmbH & Co. KG, Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany.
3Pharis Biotec GmbH, 30625 Hannover, Germany.
4Mediconomics GmbH, Misburger-Strasse 81b, D-30625 Hannover, Germany.
5Department of Chemistry, University of Patras, GR-26500 Rion-Patras, Greece.
6CBL-Patras, 26333 Patras, Greece.
7Departamento de Biología Físico-Química, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, E-28040 Madrid, Spain.
8Institute of Molecular Virology, University Hospital of Ulm, Meyerhofstrasse 1, D-89081 Ulm, Germany.
9Departamento de Química, Facultad de Farmacia, Universidad San Pablo CEU, E-28664 Madrid, Spain.
*To whom correspondence should be addressed. E-mail: frank.kirchhoff{at}uni-ulm.de
Abstract
To infect host cells, most enveloped viruses must insert a hydrophobic fusion peptide into the host cell membrane. Thus, fusion peptides may be valuable targets for developing drugs that block virus entry. We have shown previously that a natural 20-residue fragment of α1-antitrypsin, designated VIRus-Inhibitory Peptide (VIRIP), that binds to the gp41 fusion peptide of HIV-1 prevents the virus from entering target cells in vitro. Here, we examine the efficacy of 10-day monotherapy with the optimized VIR-576 derivative of VIRIP in treatment-naïve, HIV-1–infected individuals with viral RNA loads of ≥10,000 copies per ml. We report that at the highest dose (5.0 grams per day), intravenous infusion of VIR-576 reduced the mean plasma viral load by 1.23 log10 copies per ml without causing severe adverse effects. Our results are proof of concept that fusion peptide inhibitors suppress viral replication in human patients, and offer prospects for the development of a new class of drugs that prevent virus particles from anchoring to and infecting host cells.
Footnotes
Citation: W.-G. Forssmann, Y.-H. The, M. Stoll, K. Adermann, U. Albrecht, K. Barlos, A. Busmann, A. Canales-Mayordomo, G. Giménez-Gallego, J. Hirsch, J. Jiménez-Barbero, D. Meyer-Olson, J. Münch, J. Pérez-Castells, L. Ständker, F. Kirchhoff, R. E. Schmidt, Short-Term Monotherapy in HIV-Infected Patients with a Virus Entry Inhibitor Against the gp41 Fusion Peptide. Sci. Transl. Med. 2, 63re3 (2010).
