A Broad-Spectrum Antiviral Peptide Blocks Infection of Viruses by Binding to Phosphatidylserine in the Viral Envelope
Rutger D. Luteijn,
Patrique Praest,
Frank Thiele,
Saravanan Manikam Sadasivam,
Katrin Singethan,
Jan W. Drijfhout,
Christian Bach,
Steffen Matthijn de Boer,
Robert J. Lebbink,
Sha Tao,
Markus Helfer,
Nina C. Bach,
Ulrike Protzer,
Ana I. Costa,
J. Antoinette Killian,
Ingo Drexler,
Emmanuel J. H. J. Wiertz
Affiliations
Rutger D. Luteijn
Department of Medical Microbiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Patrique Praest
Department of Medical Microbiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Frank Thiele
Institute of Virology, Technical University and Helmholtzzentrum Munich, 81675 Munich, Germany
Saravanan Manikam Sadasivam
Membrane Biochemistry and Biophysics, Bijvoet Centre for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands
Katrin Singethan
Institute of Virology, Technical University and Helmholtzzentrum Munich, 81675 Munich, Germany
Jan W. Drijfhout
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Christian Bach
Institute of Virology, Technical University and Helmholtzzentrum Munich, 81675 Munich, Germany
Steffen Matthijn de Boer
Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands
Robert J. Lebbink
Department of Medical Microbiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Sha Tao
Institute for Virology, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Markus Helfer
Institute of Virology, Technical University and Helmholtzzentrum Munich, 81675 Munich, Germany
Nina C. Bach
Institute of Chemistry, Chair of Organic Chemistry II, TU Munich, 85748 Garching, Germany
Ulrike Protzer
Institute of Virology, Technical University and Helmholtzzentrum Munich, 81675 Munich, Germany
Ana I. Costa
Department of Medical Microbiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
J. Antoinette Killian
Membrane Biochemistry and Biophysics, Bijvoet Centre for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands
Ingo Drexler
Institute for Virology, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Emmanuel J. H. J. Wiertz
Department of Medical Microbiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
The ongoing threat of viral infections and the emergence of antiviral drug resistance warrants a ceaseless search for new antiviral compounds. Broadly-inhibiting compounds that act on elements shared by many viruses are promising antiviral candidates. Here, we identify a peptide derived from the cowpox virus protein CPXV012 as a broad-spectrum antiviral peptide. We found that CPXV012 peptide hampers infection by a multitude of clinically and economically important enveloped viruses, including poxviruses, herpes simplex virus-1, hepatitis B virus, HIV-1, and Rift Valley fever virus. Infections with non-enveloped viruses such as Coxsackie B3 virus and adenovirus are not affected. The results furthermore suggest that viral particles are neutralized by direct interactions with CPXV012 peptide and that this cationic peptide may specifically bind to and disrupt membranes composed of the anionic phospholipid phosphatidylserine, an important component of many viral membranes. The combined results strongly suggest that CPXV012 peptide inhibits virus infections by direct interactions with phosphatidylserine in the viral envelope. These results reiterate the potential of cationic peptides as broadly-acting virus inhibitors.