Category Nature

A group from Cornell University, Doha, Qatar, etc. has reported how much risk is there in reinfection of SARS-CoV-2.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00141-3/fulltext

Among 43,044 individuals with SARS-CoV-2 antibody-positive from Apr. 16^th to Dec. 31^th, 2020, persons with PCR-positive swab ≥14 days after the first-positive antibody test were thought to be reinfected.

As a result of this study, the efficacy against reinfection was estimated at 92.7% (95% CI: 91.3–93.9%). It is so interesting that this efficacy estimate is similar to the efficacy reported for the two mRNA COVID-19 vaccines, and reinfections were less severe than primary infections. That is good news for all of us.

A group from University of British Columbia, etc. has reported studies on  molecular structures at the binding site of the SARS-CoV-2 spike protein of N501Y variant and ACE2 receptor with using a cryo-electron microscopy.
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001237

The overall binding structure at the binding site of ACE2 and SARS-CoV-2 is almost identical to that of the unmutated version, with the exception of some local rearrangements. The aromatic ring of Y501 is sandwiched between Y41 and K353 of the ACE2 receptor, and  Y501 in the SARS-CoV-2 spike protein and Y41 in the ACE2 receptor form a perpendicular y-shaped π–π stacking interaction. This could be a reason of the increased infectivity.

The same conclusion from other researchers as this was already blogged.

A group from Max Planck Institute of Biophysics has simulated effects of ACE2 glycosylation onto binding to SARS-CoV-2 RBD.
https://www.pnas.org/content/118/19/e2100425118.long

Structurally speaking, there would be four glycosylation sites on ACE2 (N53, N90, N103, and N322）which have the possibility to interact with the RBD. The difference in glycan structures also affects binding strength to RBD, and asialo-types and high mannose show stronger interactions with the RBD at N70 and N322 positions. At the N90 position, high mannose has stronger affinity than asialo-types, and at the N322 position, vice versa.

Effects of glycans onto binding to RBD are different between N90 and N322 positions. The N90 glycan shields ACE2 from RBD binding, and the N322 glycan strengthens RBD binding, conversely. Actually, it has already reported that almost all mutations removing N322 glycosylation site are detrimental to the binding of the RBD. Since the N322 glycan interacts mainly with Y369–K378, R408, N437, N439, and V503 near the site of the N501Y mutation, it might be associated with increased ACE2 binding affinity and enhanced infectivity.

For your information, two articles related to effects of ACE2 glycosylation on to RBD binding have already introduced in this blog site.
The same thing has already demonstrated experimentally as sialic acids and high mannose weaken SARS-CoV-2 binding to ACE2.

There is an unique lectin named “SeviL” which has binding affinity to ganglioside GM1band and its precursor form, asialo-GM1.
https://www.nature.com/articles/s41598-020-78926-7

This lectin could be extracted from Septifer virgatus.
A picture below shows its cluster.
The amount of Sevil contained in one Septifer virgatus is about 0.004mg. Taking the popuration around there into consideration, there would be 100g SeviL per 10 square meters.

That day was cloudy and windy, but here is a shore where Septifer virgus is living.

A group from University of Glasgow, UK, etc. has reported a detailed studies on the relationship between glycosylation of Synovial fibroblasts(SFs) and arthritis inflammation.
https://www.nature.com/articles/s41467-021-22365-z

It is well known that glycosylation of IgG changes to agalacto types, and the expression of TNFα increases in arthritis. Authors evaluated changes in glycosylation of SFs with using lectins and MS, and confirmed that sialylation decreased in both N-glycans and O-glycans. The decrease in sialylation was observed in α-3Sia but not α-3Sia. Furthermore, levels of sialylation correlated with disease stages. And, it was shown that the decrease in sialylation seems to be induced by TNF, in contrast with IL-1 or IL-17 that had no effect.

It is so important to establish whether desialylation plays a leading role in SFs activation, or on the contrary, it is a more indirect consequence of ongoing inflammation. Authors demonstrated that α2-6Sia blocking by ST6GAL1 mRNA silencing upregulates IL-6 and CcL2. This would be a really meaningful thing relating to the therapeutic strategies.

In a figure below, CIA means Collagen-induced arthritis.

The common knowledge in HIV infection is that two types of receptors are related to the infection to CD4⁺ T cells. First of all, an envelop glycoprotein of HIV called gp120 binds to the first receptor CD4, then binds to the second receptor, CCR5 or CXCR4, and initiates membrane fusion between HIV and T cell. A group from University of Sydney, etc. has reported what major HIV target cells in human anogenital tissues in the HIV infection.
https://www.nature.com/articles/s41467-021-22375-x

Authors have identified two types of cells, one is D14⁺CD1c⁺ monocyte-derived dendritic cells（CD14⁺CD1c⁺MDDC, and the other is　Langerin-expressing dendritic cells 2（Langerin⁺ cDC2). Langerin is a C-type lectin which is selectively expressed on langerhans cells (LC), a subset of dendritic cells distributing in dermis and mucosa. The binding specificity of langerin is known to be high mannose and galactose with sulfated 6th site. Furthermore, it was found that HIV infection was correlated with Siglec-1 expression on CD14⁺ MDDC. In this way, these cells bind HIV and mediate efficient HIV uptake, and transfer to CD4⁺ T cells.

From a view point of glycan and lectin, it is so important to understand the relationship between C-type lectins on host cells and HIV gp120 glycoproteins.

A group from University of Liverpool has reported results of random forests model (one of machine learning methods) to predict the animal host of SARS-CoV-2.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009149

A figure below shows stacked bar plots of predicted probabilities of each host category for coronavirus RNA sequences, assuming bird, camelid, carnivore, human, rodent, swine, yangochiroptera, and yinpterochiroptera as potential hosts. It is clearly shown that MARS-CoV has camelid host, SARS-CoV has carnivore host, and SARS-CoV2 seems to have a bat host (suborder Yinpterochiroptera). While the random forests model supports bats as the ultimate origin of SARS-CoV-2, the involvement of intermediate hosts remains unclear.

A group from Rowan University, Stratford, USA, etc. has suggested that Maackia amurensis lectin (MAL, MAA, MASL as abbreviated names) could be effctive in inhibiting SARS-CoV-2 infection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019238/

Oral squamous cells were used as a model cell in this study. Transcriptome analysis was done to investigate effects of MAL onto ACE2, ADAM17, Furin, and Glycosyltransferases (GalNAc-T, ST6GalNAc-1, and ST6GalNAc-2）.
Interestingly, it was shown that those decreased in a MAL dose dependent manner. For instance, at a dose of 1925nM of MAL, ACE2 mRNA level decreased by 60％, ADAM17 by 40％, and ST6GalNAc-1 by 60%. As a result of these events, MAL decreases inflammatory signaling events that would otherwise lead to activation of the IL6 amplifier implicated in COVID-19 induced ARDS

MAL is known to have binding specificity to α2-3Sia.

A group from San Martino Policlinico Hospital, Genoa, Italy, etc. has reported on characteristics of bronchoalveolar lavage fluid (BALF) collected from COVID-19 patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049078/

BALF cellularity was mainly composed of neutrophils and macrophages (neutrophils were more abundant than macrophages). The median value of macrophage percentages was higher in non-survivors compared to survivors (35% vs 20%). However, we must be cautious that all the differences shown in a table below are not statistically significant.

A group from Northwest University, Xi’an, China, etc. has reported a potential glycan biomarker for Esophageal squamous cell carcinoma (ESCC)
.
https://www.frontiersin.org/articles/10.3389/fchem.2021.637730/full

Saliva was used as a sample in this study, and saliva was centrifuged to remove insoluble components and a protease inhibitor was added. Lectin microarrays using 37 lectins were used for investigating differences in glycosylation patterns between healthy volunteers (HV) and ESCC patients. As a result, it was found that DSA and ECA lectins are specific to ESCC, and Galβ1-4GlcNAc-containing N-glycans could be potential biomarkers for ESCC.