title: Synthetic Mucus Nanobarriers for Identification of Glycan-Dependent Primary Influenza A Infection Inhibitors.
abstract: Current drugs against the influenza A virus (IAV) act by inhibiting viral neuraminidase (NA) enzymes responsible for the release of budding virions from sialoglycans on infected cells. Here, we describe an approach focused on a search for inhibitors that reinforce the protective functions of mucosal barriers that trap viruses en route to the target cells. We have generated mimetics of sialo-glycoproteins that insert into the viral envelope to provide a well-defined mucus-like environment encapsulating the virus. By introducing this barrier, which the virus must breach using its NA enzymes to infect a host cell, into a screening platform, we have been able to identify compounds that provide significant protection against IAV infection. This approach may facilitate the discovery of potent new IAV prophylactics among compounds with NA activities too weak to emerge from traditional drug screens.
authors: Department of Pathology, Division of Comparative Pathology and Medicine and Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors: Miriam
authors: M
authors: Cohen
authors: Department of Pathology, Division of Comparative Pathology and Medicine and Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors: Hooman P
authors: HP
authors: Senaati
authors: Department of Pathology, Division of Comparative Pathology and Medicine and Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors: Christopher J
authors: CJ
authors: Fisher
authors: Department of Pathology, Division of Comparative Pathology and Medicine and Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors: Mia L
authors: ML
authors: Huang
authors: Department of Pathology, Division of Comparative Pathology and Medicine and Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors: Pascal
authors: P
authors: Gagneux
authors: Department of Pathology, Division of Comparative Pathology and Medicine and Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors: Kamil
authors: K
authors: Godula