title: Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin.
abstract: Highly pathogenic human coronaviruses associated with a severe respiratory syndrome, including Middle East respiratory syndrome coronavirus (MERS-CoV), have recently emerged. The MERS-CoV epidemic started in 2012 and is still ongoing, with a mortality rate of approximately 35%. No vaccine is available against MERS-CoV and therapeutic options for MERS-CoV infections are limited to palliative and supportive care. A search for specific antiviral treatments is urgently needed. Coronaviruses are enveloped viruses, with the spike proteins present on their surface responsible for virus entry into the target cell. Lectins are attractive anti-coronavirus candidates because of the highly glycosylated nature of the spike protein. We tested the antiviral effect of griffithsin (GRFT), a lectin isolated from the red marine alga Griffithsia sp. against MERS-CoV infection. Our results demonstrate that while displaying no significant cytotoxicity, griffithsin is a potent inhibitor of MERS-CoV infection. Griffithsin also inhibits entry into host cells of particles pseudotyped with the MERS-CoV spike protein, suggesting that griffithsin inhibits spike protein function during entry. Spike proteins have a dual function during entry, they mediate binding to the host cell surface and also the fusion of the viral envelope with host cell membrane. Time course experiments show that griffithsin inhibits MERS-CoV infection at the binding step. In conclusion, we identify griffithsin as a potent inhibitor of MERS-CoV infection at the entry step.
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Millet
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Séron
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Rachael N
authors.initials: RN
authors.lastname: Labitt
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Danneels
authors.affiliation: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Palmer
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Whittaker
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Dubuisson
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France. Electronic address: Sandrine.belouzard@ibl.cnrs.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Belouzard
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000821:virology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D065207:Middle East Respiratory Syndrome Coronavirus / Q000187:drug effects* / Q000502:physiology*; D037121:Plant Lectins / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001688:Biological Products; D037121:Plant Lectins; C499654:griffithsin protein, Griffithsia
keywords: Antiviral; Lectin; MERS-CoV; Virus entry