Using Lectins for Coronavirus Research
Lectins from various sources have been shown to exhibit potent antiviral properties through their direct binding to viral envelope glycans, which in turn prevents viral cell entry. Several lectins, particularly plant lectins with affinity toward mannose (Man) and N-acetylglucosamine (GlcNAc) sugar moieties have been identified as potential therapeutic agents in the prevention of viral transmission in human immunodeficiency virus (HIV) and coronaviruses (SARS-CoV and MERS-CoV) . The red alga lectin griffithsin has demonstrated antiviral activity for MERS-CoV  and the GlcNAc binding plant lectin Urtica dioica agglutinin (UDA) has been administered in vivo in a murine model of SARS-Cov infection resulting in ‘significant protection from weight loss’ and a ‘substantial therapeutic effect’ . Promising results like these have led to published appeals to consider the antiviral effects of lectins in combating SARS-CoV [6,7].
Coronaviruses are enveloped single-stranded RNA viruses that contain at least four structural proteins: the membrane (M), envelope (E), spike (S), and nucleocapsid (N) protein. There are 20-30 sites of N-glycosylation on the S protein, depending on the coronavirus , and this heavily glycosylated protein mediates virus–cell attachment and fusion. Coronavirus S protein N-glycans also mediates the activation of the antiviral innate immune response: coating transmissible gastroenteritis coronavirus (TEGV) particles with Con A prior to cellular exposure reduces interferon α (IFN-α) production [4,5]. Dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN), a mammalian expressed C-type lectin, interacts with the glycans of coronaviruses and has been shown to mediate viral entry in the case of SARS-CoV. Mannose-binding lectin (MBL) can prevent this interaction (and potentially that of others) by blocking viral binding to DC-SIGN, isolated to a single critical N-glycosylation site in SARS-CoV . MBL interferes with the coronavirus entry process by binding to the high-mannose type N-glycans of SARS-CoV via the S protein, thereby preventing viral attachment to target proteins and the host cell [2, 3]. The importance of lectins in viral defense is also illustrated by MBL deficiency, which has been postulated as a susceptibility factor for SARS-CoV . N- and O-glycosylation of either the SARS-CoV-2 spike protein or host receptor have a dramatic effect on protease cleavage of the spike protein to allow viral entry . Mannose-specific lectins targeting N-glycosylation, such as Concanavalin A and Pisum sativum, can inhibit ACE2-receptor binding domain (RBD) interactions in SARS-CoV-2 and exhibit antiviral effects .
Vector Laboratories is an established manufacturer of many plant lectins that are described in the literature as valuable research tools. Below is a list of mannose-specific and mannose/glucose-specific lectins that are available in unconjugated and conjugated formats.
- Galanthus nivalis
- Hippeastrum hybrid
- Narcissus pseudonarcissus
- Concanavalin A
- Lens culinaris
- Musa paradisiaca
- Pisum sativum
Based on prior studies of coronaviruses such as SARS-CoV, MERS- CoV, and TEGV, plant lectins (especially mannose-specific lectins) may be used to investigate the following properties of the coronavirus SARS-CoV-2, which causes COVID-19:
- Viral glycosylation properties
- Lectin-based binding inhibition and cellular entry
- Novel therapeutic strategies based on glycans and lectins
- Mitchell, C. et al. Antiviral Lectins: Selective Inhibitors of Viral Entry. Antiviral Res. 2017 Jun; 142: 37–54.
- Keyaerts, E. et al. Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle. Antiviral Res. 2007 Sep;75(3):179-87.
- Ritchie, G. et al. Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein. Virology. 2010 Apr 10;399(2):257-69.
- Fung, S. and D.X. Liu. Post-translational modifications of coronavirus proteins: roles and function. Future Virol. (2018) 13(6), 405–430.
- Charley B, et al. Glycosylation is required for coronavirus TGEV to induce an efficient production of IFN alpha by blood mononuclear cells. Scand. J. Immunol. 1991, 33(4), 435–440.
- Mazalovska M, and J.C. Kouokam. Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections. Biomed. Res. Int. 2018 May 8;2018:3750646.
- De Clercq E. Potential antivirals and antiviral strategies against SARS coronavirus infections. Expert Rev Anti Infect Ther. 2006, 4(2): 291–302.
- Millet, J.K. et al. Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin. Antiviral Res. 2016, 133, pp. 1–8.
- Kumaki, Y. et al. Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin. Antiviral Res. 2011, 90, no. 1, pp. 22–32.
- Ip, WK. et al. Mannose-binding lecting in severe acute respiratory syndrome coronavirus infection. J Infect Dis. 2005 May 15;191(10):1697-704.
Yang, Q. et al. Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration. eLife 2020;9:e61552.
Azad, T. et al. Nanoluciferase complementation-based bioreporter reveals the importance of N-linked glycosylation of SARS-CoV-2 S for viral entry. Molecular Therapy. 2021.