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.

Chicken mannose binding lectin has antiviral activity towards infectious bronchitis virus

“…Other lectins have also been reported to act during the initial stages of the infection of coronaviruses. Interestingly, while the red algae lectin griffithsin interacts directly with the spike protein of MERS-CoV (Millet et al, 2016), the same lectin showed post-binding antiviral activity during entry of many different coronaviruses in cell culture cells (O'Keefe et al, 2010).…”

Identification of anti-viral activity of the cardenolides, Na + /K + -ATPase inhibitors, against porcine transmissible gastroenteritis virus

“…The combination of Na + /K + -ATPase α and β isoforms determine the selectivity of Na + /K + -ATPase inhibition by cardenolides (Baker Bechmann et al, 2016;Habeck et al, 2016;Katz et al, 2015) and host cell receptors differ in coronaviral specific recognition and infection (Millet et al, 2016;Weiss and Navas-Martin, 2005). We then further tested whether cardenolides exert anti-MHV activity.…”

“…Many small chemical molecules exert anti-coronavirus activity via targeting either viral entry or the intracellular viral life cycle (Tong, 2009a(Tong, , 2009b. In addition, the small protein griffithsin directly targets and interacts with coronaviral spike glycoprotein to interfere with cell entry, thereby exhibiting an efficient inhibition of viral infectivity for broad spectrum of CoV, including TGEV, SARS CoV, and MERS CoV (Millet et al, 2016;O'Keefe et al, 2010). However, there has no report Toxicology and Applied Pharmacology 332 (2017)…”

Murine Leukemia Virus (MLV)-based Coronavirus Spike-pseudotyped Particle Production and Infection

“…It has been extensively used in our research on viral entry of various enveloped viruses, including VSV (Sun et al , 2008), influenza virus (Tse et al , 2014) and coronaviruses (Belouzard et al , 2009; Millet and Whittaker 2014; Millet et al , 2016). We have successfully used this method to pseudotype viral envelope glycoproteins from all three classes of viral fusion proteins: influenza hemagglutinin (HA, class I), coronavirus spike (S, class I), Ebola glycoprotein (GP, class I), Semliki forest virus (SFV) E1 (class II), and vesicular stomatitis virus (VSV) G glycoprotein (class III).…”