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Published on: October 31, 2017
Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin
Jean K Millet1, Karin Séron2, Rachael N Labitt1
1Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
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.
Insights
Griffithsin, a marine alga lectin, effectively inhibits Middle East respiratory syndrome coronavirus (MERS-CoV) infection by blocking viral entry into host cells. This discovery offers a promising new avenue for developing treatments against MERS-CoV.
Area of Science:
- Virology
- Drug Discovery
- Marine Biotechnology
Background:
- Emerging highly pathogenic coronaviruses like MERS-CoV pose significant public health threats with high mortality rates.
- Current MERS-CoV treatments are limited to supportive care, highlighting the urgent need for effective antiviral therapies.
- The spike protein of coronaviruses, crucial for cell entry, is a potential target for antiviral interventions due to its glycosylated nature.
Purpose of the Study:
- To evaluate the antiviral efficacy of griffithsin (GRFT), a lectin from the marine alga Griffithsia sp., against MERS-CoV infection.
- To investigate the mechanism by which griffithsin affects MERS-CoV entry into host cells.
Main Methods:
- Testing the antiviral effect of griffithsin against MERS-CoV in vitro.
- Assessing the cytotoxicity of griffithsin to ensure safety.
- Using pseudotyped viral particles to study griffithsin's effect on MERS-CoV spike protein-mediated entry.
- Conducting time course experiments to pinpoint the stage of viral entry inhibited by griffithsin.
Main Results:
- Griffithsin demonstrated potent inhibition of MERS-CoV infection without significant cytotoxicity.
- Griffithsin effectively blocked the entry of MERS-CoV spike protein-pseudotyped particles into host cells.
- Time course experiments indicated that griffithsin interferes with the initial binding step of MERS-CoV to host cells.
Conclusions:
- Griffithsin is identified as a potent inhibitor of MERS-CoV infection.
- Griffithsin acts by inhibiting the MERS-CoV spike protein's function during the viral entry process, specifically at the binding stage.
- This study suggests griffithsin as a promising candidate for the development of novel anti-MERS-CoV therapeutics.
