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.