COVID-19

The work measured cryo-EM structures of the S protein and in complex with a 9-O-acetylated sialic acid. Free 9-O-Ac-Me-Sia does not trigger membrane fusion and is dependent on multivalent interaction.

Efficient binding of SARS-CoV-2 to ACE2. The study revealed a furin cleavage site between S1/S2 subunits which may contribute to expanded tropism of the virus. SARS-CoV polyclonal antibodies inhibit SARS-CoV-2 entry into cells providing an outline for the design of vaccines and inhibitors.

Correspondence to the Lancet from the COVID-19 MS coalition (link) to accurately determine prognostic/diagnostic markers using serological assays. Multi-omic profiling will allow the identification of key biomarkers to help elucidate mechanism of action. Current methodologies does not factor in the spike glycoprotein and its conformational changes that is critical in immunogenic response.

The spike glycoprotein of SARS-CoV-2 was used to generate the vaccine (ChAdOx1 nCoV-19) which was immunogenic in mice. A single vaccination in rhesus macaque elicited both humoural and cellular immune responses.

Early epidemiological studies have shown age to be a critical factor in disease severity. Pre-existing conditions such as diabetes, CVD and hypertension all involving a glycan component is associated with increased mortality. Environmental factors through epigenetic can significantly alter glycan composition and alter biological age. This could serve as a biomarker for COVID-19 risk and mortality.

The highly glycosylated coronavirus spike protein selectively binds to the receptor of ACE2. Epidemiological analysis in a hospital in Hong Kong revealed blood group O associated with a low risk of infection. The study investigated whether natural antibodies of the ABO system can be used to effectively block binding site of the S glycoprotein of SARS-CoV. It was observed that anti-A antibodies inhibited adhesion between S glycoprotein and ACE2 receptor, indicating these antibodies may block interaction between the virus and receptor.

The endoplasmic reticulum is a key machinery used by viruses to produce correctly folded glycoproteins. Iminosugars with glucose stereochemistry are excellent inhibitors of glucosidases which are involved protein folding and stability. Inhibition leads to glycoprotein misfolding and preventing viral replication.

In humans, the ability to produce the glycan with terminal Alpha-gal moiety has led to the development of a protective response against this antigen in humans. The alpha-Gal structure is prevalent in pathogenic viruses and other organisms which elicits a humoural immune response utilizing IgM/IgG antibodies. The researchers postulate that immune response to alpha-Gal can mediate COVID-19 severity. The authors conclude that inhibition of the alpha-Gal induced immune response can lead to increased viremia and disease severity. Supply of alpha-Gal probiotics may reduce severity of COVID-19.

Docking studies have shown that putative heparin/heparan sulfate binding site is adjacent to the ACE2 binding domain. In vitro studies show that binding of ACE2 and heparin occurs independently. This supports a model where SARS-CoV-2 infection occurs through a complex between heparan sulfate and ACE2.