A group from Universidade CEUMA, Brazil, etc. has reviewed past instances using lectin–glycan interactions to combat enveloped viruses, and mentioned about challenge to SARS-CoV-2.
https://academic.oup.com/glycob/article/31/4/358/5934657
The presence of glycoproteins in the viral envelope opens a wide range of possibilities for application of lectins to fight COVID-19. Lectins could be leading molecules for the development of new antiviral drugs due to their ability to inhibit viral entry into the host cell by binding to glycans expressed on he virus envelop.
The overall view of glycosylation profiles of SARS-CoV-2 is as follows. There are 22 N-glycosylation sites and 6 O-glycosylation sites on the spike protein. The oligomannose-type glycans are predominant in two sites (N234 and N709). Complex-type glycans are predominantly expressed in 14 amino acid residues (N17, N74, N149, N165, N282, N331, N343, N616, N657, N1098, N1134, N1158, N1173 and N1194), while six sites show a mixture of oligomannose- and complex-type glycans (N61, N122, N603, N717, N801 and N1074). The most common configuration of oligomannose-type glycans was Man5GlcNAc2. The short O-glycans such as Tn and core 1 structures are mainly expressed in 6 sites (T73, T76, T478, T676, T678, T1076).
Typical lectins evaluated as antiviral drugs are explained in the review paper (FRAIL, GRFT, Cyanovirin-N, BanLec, MVN, and Avaren). All of these lectins have binding specificity to oligo and high mannose, probably because envelopes of targeted viruses in the past (e.g., HIV, HCV, influenza, and Ebora) were heavily mannosylated. In that sense, we can say that glycosylation profile of SARS-CoV-2 is somewhat different from other enveloped viruses, and therefore, there might be more suitable lectins for SARS-CoV-2 besides those lectins.
Anyhow, the major limitation in using lectins as therapeutic drugs is the possible binding of the lectin in unwanted glycosylated targets. For instance, the administration of lectins could result in the agglutination and proliferation of cells. Therefore, it is so important to modify lectins with using protein engineering to suppress such side effects and to extract only the antiviral property against SARS-CoV-2. Probably, the key word would be making fusion proteins, e.g., fusion to Fab, fusion to Fc, PEGylation, and so forth.