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Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin.
Antiviral Res. 2016 09; 133:1-8.AR

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+Show Affiliations

Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.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.Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.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.Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27424494

Citation

Millet, Jean K., et al. "Middle East Respiratory Syndrome Coronavirus Infection Is Inhibited By Griffithsin." Antiviral Research, vol. 133, 2016, pp. 1-8.
Millet JK, Séron K, Labitt RN, et al. Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin. Antiviral Res. 2016;133:1-8.
Millet, J. K., Séron, K., Labitt, R. N., Danneels, A., Palmer, K. E., Whittaker, G. R., Dubuisson, J., & Belouzard, S. (2016). Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin. Antiviral Research, 133, 1-8. https://doi.org/10.1016/j.antiviral.2016.07.011
Millet JK, et al. Middle East Respiratory Syndrome Coronavirus Infection Is Inhibited By Griffithsin. Antiviral Res. 2016;133:1-8. PubMed PMID: 27424494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin. AU - Millet,Jean K, AU - Séron,Karin, AU - Labitt,Rachael N, AU - Danneels,Adeline, AU - Palmer,Kenneth E, AU - Whittaker,Gary R, AU - Dubuisson,Jean, AU - Belouzard,Sandrine, Y1 - 2016/07/15/ PY - 2016/03/24/received PY - 2016/06/20/revised PY - 2016/07/13/accepted PY - 2016/7/19/entrez PY - 2016/7/19/pubmed PY - 2017/11/29/medline KW - Antiviral KW - Lectin KW - MERS-CoV KW - Virus entry SP - 1 EP - 8 JF - Antiviral research JO - Antiviral Res. VL - 133 N2 - 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. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/27424494/Middle_East_respiratory_syndrome_coronavirus_infection_is_inhibited_by_griffithsin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(16)30172-3 DB - PRIME DP - Unbound Medicine ER -