Plant lectins as prospective antiviral biomolecules in the search for COVID-19 eradication strategies

Abstract

Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19. Lectins have binding affinity to the glycans of SARS-COV-2 Spike glycoprotein that has N-glycosylation sites. Apart from this, the complement lectin pathway is a "first line host defense" against the viral infection that is activated by mannose-binding lectins. Mannose-binding lectins deficiency in serum influences innate immunity of the host and facilitates infectious diseases including COVID-19. Our accumulated evidence obtained from scientific databases particularly PubMed and Google Scholar databases indicate that mannose-specific/mannose-binding lectins (MBL) have potent efficacies like anti-infectivity, complement cascade induction, immunoadjuvants, DC-SIGN antagonists, or glycomimetic approach, which can prove useful in the strategy of COVID-19 combat along with the glycobiological aspects of SARS-CoV-2 infections and antiviral immunity. For example, plant-derived mannose-specific lectins BanLac, FRIL, Lentil, and GRFT from red algae can inhibit and neutralize SARS-CoV-2 infectivity, as confirmed with in-vitro, in-vivo, and in-silico assessments. Furthermore, Bangladesh has a noteworthy resource of antiviral medicinal plants as well as plant lectins. Intensifying research on the antiviral plant lectins, adopting a glyco-biotechnological approach, and with deeper insights into the "glycovirological" aspects may result in the designing of alternative and potent blueprints against the 21st century's biological pandemic of SARS-CoV-2 causing COVID-19.

Keywords: Antiviral plant lectins; Glycobiotechnology; Glycoprotein; Glycosylation; Mannose-specific/mannose-binding lectins; SARS-CoV-2 glycobiology.

Graphical abstract

Fig. 1

“Schematic representation of viral infection (A) and the role of cyanobacterial lectin, cyanovirin (CV-N) on inhibition of viral entry and fusion (B). CV-N blocks the interaction between the viral gp120 and the CD4 receptor on the host cell. It prevents the interaction with the associated co-receptors CXCR4/CCR5. As a consequence, the virus cannot enter into the cell.”

Fig. 2

“Diagram of SARS-CoV-2 entry into host cells. S protein binding to ACE2 receptor and virus attachment to the cell; S protein cleaved by TMPRSS2 produces S1 and S2 subunits. HR1 and HR2 of the S2 subunit gradually approach each other and form a six-helix bundle (6-HB), which causes the virus envelope and host cell membrane to complete fusion.”

Fig. 3

“Complement pathways in SARS-CoV-2 infection. The activation of the classical pathway occurs through the C1 complex, after recognition of antibodies complexed to SARS-CoV-2. This leads to the cleavage of the C2 component into C2a and C2b. C2a joins the common pathway of the three complement pathways to form the C3 convertase. After binding of MBL/MASP complexes to the surface of pathogens, MASP-1 autoactivates, transactivates MASP-2, and C2 and C4 components are cleaved (C2 and C4 by MASP-2 and C2 by MASP-1), generating the C3 convertase. The alternative pathway is initiated by the spontaneous hydrolysis of component C3, generating C3a and C3b. C3b binds to factor B and is cleaved by factor D, forming the C3 convertase of the alternative pathway. After this step, the three pathways converge into a single pathway. The C3 convertase enzyme cleaves component C3 into C3a and C3b. C3a and C4a are anaphylatoxins that contribute to an increase in inflammatory processes and to the chemotaxis of neutrophils and macrophages (red arrows), while C3b performs viral opsonization. The formation of C5 convertase occurs in different ways through the three pathways, but all generate C5a and C5b. C5a is an anaphylatoxin (as also C3a) that contributes to inflammatory processes, and regulates innate and adaptive immune responses , while C5b joins the last C6-C9 components of the cascade and forms the membrane attack complex.” (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

“MBL binding and complement activation enhances phagocytosis by acting as an opsonin.”