How glycobiology can help us treat and beat the COVID-19 pandemic

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge during the last months of 2019, expanding throughout the world as a highly transmissible infectious illness designated as COVID-19. Vaccines have now appeared, but the challenges in producing sufficient material and distributing them around the world means that effective treatments to limit infection and improve recovery are still urgently needed. This review is focused on the relevance of different glycobiological molecules that could potentially serve as or inspire therapeutic tools during SARS-CoV-2 infection. As such, we highlight the glycobiology of the SARS-CoV-2 infection process, where glycans on viral proteins and on host glycosaminoglycans have critical roles in efficient infection. We also take notice of the glycan-binding proteins involved in the infective capacity of virus and in human defense. In addition, we critically evaluate the glycobiological contribution of candidate drugs for COVID-19 therapy such as glycans for vaccines, anti-glycan antibodies, recombinant lectins, lectin inhibitors, glycosidase inhibitors, polysaccharides, and numerous glycosides, emphasizing some opportunities to repurpose FDA-approved drugs. For the next generation drugs suggested here, biotechnological engineering making new probes to block the SARS-CoV-2 infection might be based in the essential glycobiological insight on glycosyltransferases, glycans, glycan-binding proteins and glycosidases related to this pathology.

The glycosylation in SARS-CoV-2 and its receptor ACE2

“… 409 , 410 GalNAc-O-Ser/Thr (Tn antigen) and Gal-GalNAc-O-Ser/Thr (T antigen) are well-known natural antigens and associated with the pathogenesis of many diseases. 411 – 413 Compared to non-infected individuals, the anti-Tn antibodies level in COVID-19 patients are significantly lower, suggesting that natural anti-Tn antibodies may be protective against COVID-19. 414 In addition, the HIV-1 Env Fab-dimerized glycan (FDG)-reactive antibodies are an anti-glycan antibody that recognize high mannose glycans of SARS-CoV-2, indicating the potential prospects of these natural antibodies in SARS-CoV-2 treatment.…”

Profile of Immunoglobulin G N-Glycome in COVID-19 Patients: A Case-Control Study

“…The transmembrane S protein is extensively glycosylated with a total of 22 N-linked glycan sequons per protomer which mediate infectivity and immune escape (3,4). While understanding that the glycan structures of SARS-CoV-2 potentially assist vaccines design, antibody therapeutics, screening of small-molecule drugs and their targets (5)(6)(7), and recognition of the human immunoglobulin G (IgG) glycome hold the similar relevance to investigate the susceptibility and complicated clinical phenotypes of the SARS-CoV-2 infection.…”

Non-neutralizing SARS CoV-2 directed polyclonal antibodies demonstrate cross-reactivity with the HA glycans of influenza virus

“…These glycans are immunogenic in nature and are reported to elicit potent neutralizing antibodies in the case of HIV-1 (2G12) [27] and SARS-CoV-2 spike protein (S309) [28] . In SARS-CoV-2, glycosylation of the spike protein is essential for viral infection and is important for viral escape and defence mechanisms [29] . The shedding of viral glycoproteins can redirect the humoral immune response by exposing immunodominant (non-neutralizing) epitopes, not exposed on the functional native closed trimeric conformation of the Env proteins, which plausibly leads to the production of cross-reactive binding antibodies which are, however, non-neutralizing [3] , [30] .…”