Infectious disease

Cell culture and rat studies identified lipopeptide-based inhibitors of MERS-CoV S protein, Ebola virus glycoprotein and HIV env that could help treat Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus, HIV and influenza virus infections. Structure-based design, chemical synthesis and testing in human liver cell line-based activity assays of lipopeptide analogs of a conserved region of the viral fusion proteins MERS-CoV S protein, Ebola virus glycoprotein, HIV env and HA yielded three compounds that inhibited MERS-CoV S protein-mediated cell-cell fusion with EC₅₀ values of 0.1, 0.11 and 0.52 μM, respectively. In Ebola virus- or HIV-infected HeLa cells, one of the compounds inhibited Ebola virus glycoprotein-mediated viral entry and HIV env-mediated cell-cell fusion with EC₅₀ values of 1.02 and 3.63 μM, respectively. In HEK cells infected with one of two Tamiflu oseltamivir-resistant influenza A strains or an influenza B strain, the compound inhibited viral replication with EC₅₀ values of 1.87-4.36 μM. In a canine kidney cell line infected with one of two additional influenza A strains, the three compounds inhibited viral replication with EC₅₀ values of 0.7-12.9 μM. Next steps could include optimizing and testing the compounds in additional models of viral infections...