Randomly Selected Hydrophobic Peptides Inhibit Lassa Pseudovirus

Lassa fever is a hemorrhagic fever endemic in West Africa. Currently the only available treatment, ribavirin, is only effective in the early stages of infection. Due to the limited efficacy of ribavirin, new drugs are needed to combat Lassa fever. In recent years many peptides have been developed as entry inhibitors against numerous viruses. Many of these peptides share a common trait; they are somewhat hydrophobic and have a tendency to partition into membranes. It is hypothesized that many of these peptides disrupt the physical chemistry of the membrane, inhibiting the virus from fusing with the host cell. In this study hydrophobic membrane interacting peptides were selected and challenged against a Lassa pseudovirus. This pseudovirus is composed of an HIV core (pSG3Δenv) and the Lassa envelop (Josiah strain), and allows us to study the virus, a BSL-4 pathogen, in a BSL-2 environment. Infection of the pseudovirus was detected using TZM HeLa cells, a cell line containing a gene that encodes luciferase which is promoted by tat, an HIV core protein. Initially ten hydrophobic peptides were selected; nine of which were discovered for characteristics other than antiviral activity. Interestingly, some were found to inhibit the virus while others increased viral activity. Of the peptides that inhibited the virus, the two peptides that showed the greatest antiviral activity were discovered from the same peptide library. More peptides from that library were then tested against the Lassa pseudovirus, most of which showed antiviral activity and low toxicity. In the next phase of this work these peptides will provide an archetype for the design of a combinatorial peptide library to optimize Lassa viral entry inhibition.