Archive 21/2/16

A group of NIH has reported the effects of O-glycan modification around the furin cleavage site of the new coronavirus (SARS-CoV-2) to the increased infectivity of the UK variant (B.1.1.7).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872346/

At the S1/S2 boundary of SARS-CoV-2 S-protein, an unique sequence of 4 amino acids (PRRA) is inserted forming the furin cleavage site as shown below.

S673, T676 are the positions where O-glycans are modified, as shown above. The presence of proline at 681 was deeply related to O-glycan modification at those positions. The authors also found that GALNT1 is the most active one glycosylating the furin proximal region among glycosyltransferase GALNT family. Furthermore, addition of O-glycans was shown to significantly suppress the cleavage at the furin cleavage site into S1 and S2. The UK variant (B.1.1.7) has a mutation called P681H, which replaces proline with histidine. Based on the above mentioned results, it is inferred that the non-presence of proline at 681 in UK variant suppresses O-glycan modification, resulting in increased cleavage efficiency and increased infectability.

A group from Juntendo University etc. has found antibodies (IgG) against the S-protein of the new coronavirus (SARS-CoV-2) from bovine milk whey.

https://www.sciencedirect.com/science/article/pii/S0958694621000303?via%3Dihub

The bovine milk was prepared from New Zealand cows in November 2018 and August 2019, and they discovered the presence of IgG for RBD present in the S-protein of SARS-CoV-2 from the bovine milk whey. The genome sequence of the S-protein is shown below, and the epitope mapping of the IgG shows that RBD is the one. Therefore, IgG enriched from milk whey may show neutralize activity against SARS-CoV-2.
However, this bovine milk whey was milked before the spread of COVID-19, and it is difficult to think that the cows were infected with SARS-CoV-2, and it might have been infected with an unknown coronavirus that shares immunogenicity of SRAS-CoV-2.

A group from Chinese Center for Disease Control and Prevention, Beijing etc. has infected gastric epithelial cells (GES-1) with Helicobacter pylori isolated from patients with different diseases, and investigated changes in glycan modification with lectin microarrays.
https://www.mdpi.com/2076-0817/10/2/168/htm

Patient’s disease states from which H. pylori bacteria were isolated were as follows:
Chronic gastritis (YN4-62),
Duodenal ulcer disease (M84, P164),
Gastric cancer (HLJ011, HLJ030),

The trend is characterized by the increase in α1-2Fuc and α2-3Sia modifications. GES-1 which was not infected with H. pylori, was used as a control, to compare changes in glycan expression levels. Red indicates increased ones.

Lactoferrin is an iron-binding glycoprotein with a molecular weight of 80,000 contained in milk. It is found in mammalian milk (especially colostrum), including human, but is also found in tears, saliva, pancreatic fluid and other exocrine fluids and neutrophils in adults. Lactoferrin is also known to maintain and improve health, including immune regulation, antiviral function,
lactobacillus bifidus proliferation, iron absorption regulation associated with iron binding ability, anti-inflammatory action, and lipid metabolism improvement action.

A group from University of Arizona, Tucson etc. has reported that lactoferrin actually shows antiviral effects against SARS-CoV-2, and what is the mechanism behind it.
https://www.tandfonline.com/doi/full/10.1080/22221751.2021.1888660

Using ACE2 overexpressed 293 T cells, Vero E6 cells, and Calu-3 cells, they show the inhibitory activity of lactoferrin on infection of SARS-CoV-2 in vitro. They have also verified using a molecular docking method that the mechanism of infection inhibition is blocking SARS-CoV-2 binding to heparan sulfate, which is a co-receptor of ACE2. Heparan sulfate has a negative charge and is thought to bind to a positively charged region (17 to 41 rest regions) present in the NTD of the SARS-CoV-2 S-protein. In the figures below, BLF=Bovine lactoferrin and HLF=Human lactoferrin. The lower right hand side figure shows a molecular docking image of heparin dp4 with bovine lactoferricin.

A group from Anschutz Medical Center, University of Colorado etc. has analyzed why does the SARS-CoV-2 (20I/501Y. V1) UK variant increase its infectability? using a molecular docking method.
https://www.biorxiv.org/content/10.1101/2021.02.02.428884v1.full

Comparing with the wild type N501, RBD of the mutant Y501 binds to ACE2 about 10 times more tightly, because a new hydrogen bond is formed between RBD and ACE2 (bold dashed line in the figure below), and there is a ring-ring interaction (light dashed line in the figure below).

A group from the University of Florida etc. has found that people with vitamin D deficiency were five times more likely to be infected with COVID-19 than people without deficiency after adjusting for age groups (OR = 5.155; 95％CI、3.974–6.688; P <0.001）from a statistical study using total population of 987,849 people. Healthy diets is the base of health. Sorry for the very short blog article.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716744/