Activated Platelet-Derived Antimicrobial Peptides Exhibit Virucidal Properties against Vaccinia Virus in Plasma.

Contamination of blood and blood components by bacteria, virus, fungi and parasites is a major safety risk in transfusion medicine. While there has been a tremendous success in inactivating virus contamination in blood products through UV-irradiation, new and novel proof-of-concepts for microbial reduction that enhance risk to benefit ratio of the treated products are still a public health need in transfusion medicine. In the present study, we tested four novel synthetic antimicrobial peptides originating from thrombin-induced human platelet-derived antimicrobial proteins named PD1-PD4 against an enveloped virus, Vaccinia Virus (VV) spiked in plasma as a model system. We have recently shown these peptides to be useful in reducing bacterial burden in plasma and platelets. These short synthetic peptides are human platelet-derived and known to cause no immune response in humans and non-hemolytic in nature as reported by others.

The PD1-PD4 peptides were tested on plasma samples spiked with 10-fold dilutions of the wild-type lab strain of Vaccinia Virus (WR strain). Each spiked sample was pre-incubated individually with a peptide (PD1-PD4) for 1 hour at 37°C. Spiked sample without any peptide was included as control. A cell culture-based standard plaque reduction assay method was utilized to monitor the virucidal effectiveness of the peptides. Minimal inhibitory concentration of the peptides was also estimated by testing the peptides at doubling dilutions of 100 μg/ml, 50 μg/ml, 25 μg/ml and 12.5 μg/ml concentrations.

Our analysis revealed that peptides PD3 and PD4 were potent against vaccinia virus resulting in reduction of viral titers in the plasma. PD3 peptide demonstrated the highest virucidal activity by bringing about a 2-log reduction of VV titers. PD4 peptide treatment resulted in a 1-1.5 log reduction in viral titers. The minimal inhibitory concentration analysis revealed that at 50 μg/ml concentration both the PD3 and PD4 were able to bring about a log reduction in viral titers.

The present study reports a novel antiviral agent for reducing vaccinia virus contamination in plasma. Safety profiles of these peptides as reported by others in conjunction with our current studies, provide a new proof-of-concept that could be useful as safer and simpler alternatives to the viral reduction agents in transfusion medicine.

The findings and conclusions in this abstract have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.

No relevant conflicts of interest to declare.