Saba Siddiqui¹ and Armin Ahmed²*

¹Associate Professor and Head, Department of Agriculture, Integral Institute of Agricultural science and technology (IIAST), Lucknow, India

*Corresponding Author: Armin Ahmed, Associate Professor, Department of Critical Care Medicine, King George Medical University, Lucknow, India. E-mail: drarminahmed@gmail.com

Received: December 09, 2021; Published: January 27, 2022

Abstract

>Griffithsin is a red algal protein with promising broad-spectrum antiviral action. It exists as a homodimer, and every monomer has three monosaccharide binding sites arranged as an equatorial triangle. It acts in the early part of the viral disease by hampering viral entry inside the cell. Envelop protein of many viruses shows rich glycosylation with mannose which binds with monosaccharide binding sites of Griffithsin in a multivalent binding fashion, thus bringing changes that interfere with the host cell invasion. Previous in-vitro and in-vivo studies on SARS-CoV and MERS-CoV have shown excellent inhibitory action on these viruses with no or minimal toxicity. It has also been studied for its synergistic antiviral action with Carrageenan (another algal derivative) and EK1 (a pan-coronavirus fusion inhibitor). There is growing interest in Griffithsin as a prophylactic and therapeutic option for the current COVID 19 pandemic due to its potent action, topical application causing inhibition of viral entry, safety profile, chemical stability, easy large-scale production, and synergistic action with other antiviral agents.

Keywords: Griffithsin; Coronaviruses; SARS-CoV; SARS-CoV-2

References

1. Cragg GM and Newman DJ. “Drugs from nature: past achievements, future prospects”. Advances in Phytomedicine 1 (2002): 23-27.
2. Lusvarghi S and Bewley CA. “Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential”. Viruses 10 (2016): 296.
3. Waaland SD and Watson BA. “Isolation of a cell-fusion hormone from Griffithsia pacifica kylin, a red alga”. Planta 5 (1980): 493-497.
4. https://www.who.int/emergencies/diseases/novel-coronavirus-2019
5. Mori T., et al. “Isolation and characterization of griffithsin, a novel HIV-inactivating protein, from the red alga Griffithsia sp”. Journal of Biological Chemistry 10 (2005): 9345-9353.
6. Swanson MD., et al. “A lectin isolated from bananas is a potent inhibitor of HIV replication”. Journal of Biological Chemistry12 (2010): 8646-8655.
7. O'Keefe BR., et al. “Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin”. Antimicrob Agents Chemother 47.8 (2003): 2518-2525. doi:10.1128/aac.47.8.2518-2525.2003
8. Janahi EMA., et al. “Bioengineered intravaginal isolate of Lactobacillus plantarum expresses algal lectin scytovirin demonstrating anti-HIV-1 activity”. Microbial Pathogenesis 122 (2018): 1-6.
9. Huskens D., et al. “Microvirin, a novel alpha (1,2)-mannose-specific lectin isolated from Microcystis aeruginosa, has anti-HIV-1 activity comparable with that of cyanovirin-N but a much higher safety profile”. Journal of Biological Chemistry 32 (2010): 24845-24854.
10. Ziółkowska NE., et al. “Domain-swapped structure of the potent antiviral protein griffithsin and its mode of carbohydrate binding”. Structure 7 (2006): 1127-1135.
11. Ziółkowska NE., et al. “Crystallographic, thermodynamic, and molecular modeling studies of the mode of binding of oligosaccharides to the potent antiviral protein griffithsin”. Proteins 3 (2007): 661-670.
12. Lee C. “Griffithsin, a Highly Potent Broad-Spectrum Antiviral Lectin from Red Algae: From Discovery to Clinical Application”. Marine Drugs10 (2019): 567.
13. Ishag HZ., et al. “Griffithsin inhibits Japanese encephalitis virus infection in vitro and in vivo”. Archives of Virology2 (2013): 349-358.
14. Lo MK., et al. “Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge”. Journal of Infectious Diseases 221 (2020): S480-S492.
15. Payne S. “Family Coronaviridae”. Viruses (2017): 149-158.
16. O'Keefe BR., et al. “Broad-spectrum in vitro activity, and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family Coronaviridae”. Journal of Virology10 (2010): 5456.
17. Walls AC., et al. “Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein”. Cell 2 (2020): 281-292.e6.
18. Millet JK., et al. “Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin”. Antiviral Research 133 (2016): 1-8.
19. Tang R., et al. “Porcine deltacoronavirus infection is inhibited by Griffithsin in cell culture”. Veterinary Microbiology 264 (2022): 109299.
20. Cai Y., et al. “Griffithsin with A Broad-Spectrum Antiviral Activity by Binding Glycans in Viral Glycoprotein Exhibits Strong Synergistic Effect in Combination with A Pan-Coronavirus Fusion Inhibitor Targeting SARS-CoV-2 Spike S2 Subunit”. Virology Sinus6 (2020): 857-860.
21. Girard L., et al. “Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primates”. Scientific Reports1 (2018): 8059.
22. Barton C., et al. “Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses”. Viruses12 (2016): 331.
23. Levendosky K., et al. “Griffithsin and Carrageenan Combination To Target Herpes Simplex Virus 2 and Human Papillomavirus”. Antimicrobial Agents and Chemotherapy 12 (2015): 7290-7298.
24. Alsaidi S., et al. “Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model”. Marine Drugs8 (2021): 418.
25. Vafaee Y., et al. “A modular cloning toolbox for the generation of chloroplast transformation vectors”. PLoS One10 (2014): e110222.
26. Giomarelli B., et al. “Recombinant production of anti-HIV protein, griffithsin, by auto-induction in a fermenter culture”. Protein Expression and Purification 1 (2006): 194-202.
27. Decker JS., et al. “Low-Cost, Large-Scale Production of the Anti-viral Lectin Griffithsin”. Frontiers in Bioengineering and Biotechnology 8 (2020): 1020.
28. Kramzer LF., et al. “ “Preformulation Characterization of Griffithsin, a Biopharmaceutical Candidate for HIV Prevention”. AAPS PharmSciTech3 (2021): 83.

Citation

Citation: Saba Siddiqui and Armin Ahmed. “Griffithsin; A Potential Therapeutic Agent for SARS-CoV-2". Acta Scientific Microbiology 5.2 (2022): 82-87.

Copyright

Copyright: © 2022 Saba Siddiqui and Armin Ahmed. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.