Category: Nature

Four types of coronavirus (OC43, HKU1, NL63 and 229E) are known as coronaviruses that cause common human colds. On the other hand, there are three types of coronaviruses (SARS-CoV, SARS-CoV-2, MERS-CoV) that are highly pathogenic. As you know, SARS-CoV-2 is the new coronavirus that caused the pandemic (COVID-19) from the end of 2019.

A group of Univ. of Washington etc. has report on neutralize antibodies that respond broadly to this type of β-coronaviruses.
https://www.biorxiv.org/content/10.1101/2020.12.29.424482v2.full

The cross-reaction of antibodies is a well-known phenomenon, but for example, antigen testing using antibodies does not accurately identify antigen viruses when there is such a cross-reactivity. However, a strong cross-reactivity can help inhibit the infection of new viruses if the antibodies of past-affected viruses are still active.
A monoclonal antibody against coronavirus, which was named as B6, has a wide range of cross-reactivity and is attracting attention as a neutralize antibody. As shown in the figure below, this B6 antibody has an amino acid sequence common to these β-coronaviruses in the S2 sub unit as an epitope, and the relevant part is involved in membrane fusion in the event of infection. The MHV in binding curve in the figure below is a mouse hepatitis virus belonging to the coronavirus family.

It has already been shown that the new coronavirus (SARS-CoV-2) has 22 N-type glycan modification sites (see, for example, https://science.sciencemag.org/content/369/6501/330.long).

Since SARS-CoV-2 binds strongly to ACE2 receptors, the binding strength of Mannose and GlcNAc-specific lectins was evaluated with molecular docking and molecular dynamic simulation, targeting the glycan (Man3GlcNAc2Fuc) present in RBD’s Asn343 in the S1 sub unit of the S protein, and evaluated its potential as an antiviral reagent.
https://pubmed.ncbi.nlm.nih.gov/33292056/

The lectins compared were as follows, and BanLec showed the highest binding strength.
BanLec: -105.99kcal/mol
NPA: -79kcal/mol
GRFT: -73.7kcal/mol
CV-N: -67.3kcal/mol
UDA: -98.3kcal/mol

Lectins, however, generally show side effects such as mitogenicity, hemagglutination, inflammation, etc., so confirmation with in vivo is essential.

The new coronavirus (SARS-CoV-2) is an RNA virus, but this type of virus generally results in an average of around 23 genetic mutations per year.

A group of Univ. College London has reported interesting findings on the effects of convalescent plasma treatment on the evolution of SARS-CoV-2 virus populations in patients with immunodeficiency COVID-19.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781345/

For the treatments of COVID-19, Remdesivir and convalescent plasma are used, the former is administered 41 days, 54 days after onset, the latter is administered 63 days, 65 days, and on the 93rd, both are administered.
(For the therapeutic effect of convalescent plasma, there have already been a report that there is no significant difference in clinical condition or overall mortality, for example, see the paper below.)
https://pubmed.ncbi.nlm.nih.gov/33232588/)

As shown in the figure below, it is shown that the mutation of the virus population changes very dynamically by the administration of the convalescent plasma. It seems to show that the RNA virus is easy to mutate so much, and evacuate from the convalescent plasma administration.

A group of Univ. of Southampton has investigated the effects of ACE2 glycan modification on the binding of S-protein of the new coronavirus (SARS-CoV-2) onto its infection receptor ACE2 .
https://www.sciencedirect.com/science/article/pii/S0022283620306872?via%3Dihub

By adding ST6 to WT ACE2 to increase sialic acid,
By adding Sialidase to WT ACE2 to cleave sialic acid,
By adding Kinfunensine to WT ACE2 to modify the glycan structure to Man9GlcNAc2 mainly,
By adding EndoH to WT ACE2 to remove N-type sugar chains,
By adding Fucosidase to WT ACE to remove Fuc,
and the binding of S-protein to ACE2 (Kd value) was measured by SPR.

When the N-glycans are removed from ACE2, the binding force is slightly increased, but the effect is limited.
Fuc modification of ACE2 has little effect.
Sialic acid modification of ACE2 does not seem to affect the infectivity, rather weaken the infectivity.
High mannose modification on ACE2 seems to weaken the infectivity slightly.

When the new coronavirus (COVID-19) becomes severe, cytokine storms occur and develop acute respiratory distress syndrome (ARDS). For this treatment, from the viewpoint of immune control, il-6 inhibitors such as tocilizumab (actemula) and steroids that suppress inflammation are used.

The Yale School of Medicine group reports from randomized, placebo-controlled trials that systemic corticosteroids are more therapeutic and the effects of tocilizumab are not clear.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781335/

As shown in the figure below, the behavior of covid-19 biomarkers is very different between corticosteroids and tocilizumab. Perhaps, it is because the effect is limited even if a single cytokine is inhibited.

A group of University College London has reported on the prognostic symptoms of the new coronavirus (COVID-19).
https://f1000research.com/articles/9-1349/v1

Ms analysis of 96 inflammatory and anti-inflammatory protein panels suggests that changes remain in inflammatory biomarkers and stress-induced biomarkers for more than 40 days after suffering from COVID-19.
Specifically, it is said that the effects of the following six biomarkers remain after the disease.

peroxiredoxin 3 (PRDX3)
carbamoyl phosphate synthase (CPS1)
N-Myc downstream regulated gene 1 (NDRG1)
Collagen triple helix repeat containing 1 (CTHRC1)
Cystatin C (CYTC)
Progranulin (GRN)

A group of The Memorial Hospital Group, Istanbul, Turkey groups has made an interesting report that urine foaming can be an effective indicator for diagnosing and predicting the prognosis of COVID-19.
http://www.nclin.ist/jvi.aspx?un=NCI-42027&volume=

The urine of patients hospitalized for COVID-19 or in ICU was reddish from orange in color, and the new coronavirus was diagnosed by collecting urine with a test tube and observing the foaming condition after shaking for 15 seconds.
The accuracy of the diagnosis was 92% sensitivity and 89% specificity.

The urine of healthy people is usually light yellow to light yellow-brown, and there is no basic problem if urine bubbles disappear shortly after urination.
However, it is well known that the color of urine changes with the disease state, and
when urobilinogen, urine protein and urine sugar in the urine increase, it becomes more foamy.

It may be reasonable to think of it as a reference only.

A group of Univ. of Virginia Health System has reported interesting phenomena on the expression of IgG, IgA, and IgM in the new coronavirus (COVID-19).
https://www.medrxiv.org/content/10.1101/2020.12.05.20244541v1

IgG, IgM, and IgA are highly expressed as COVID-19 becomes severe.
IL-10 and IgG inversely correlate.

Cytokine IL-10 is usually thought to be an anti-inflammatory one.
IL-10 and IgG are inversely correlated, and moreover, IgG is highly expressed as the disease becomes severe,
Does this mean that IL-10 works as an inflammatory cytokine?

Lectins with ricin B chains are collectively referred to as R-type lectins.
Ricin is galactose-specific, but the ricin-like structure has an extremely wide biological distribution and has various specificities such as sialic acid, mannose, xylose, etc. in addition to galactose.
The R-type lectin "Sevil" from mussel Mytilisepta virgata binds particularly strongly to the asialo-GM1 structure.
From the Yokohama City University Group,
https://www.nature.com/articles/s41598-020-78926-7

Dendritic cells (DCs) are at the forefront of the immune reaction.
When pathogens such as viruses invade, Toll-like receptors (TLR) and C-type lectin receptors (CLRs) expressed on DCs recognize the molecular structure peculiar to pathogens and trigger immune responses.
The CLR of DCs includes DCIR/CD367/CLEC4A, DECTIN1/CD369/CLEC7A, DECTIN2/CLEC6A, DNGR1/CD370/CLEC9A, MMR/CD206, DEC205/CD205, DC-SIGN/CD209, langerin/CD207, BDCA2/CD303/CLEC4C, etc.
The function of these lectins remain largely unknow, but for example,
DCIR binds to high mannose/fucose glycans and works inhibitory on the secretion of IL12 and TNFα, while DECTIN1 recognizes β-1,3-glucans and conversely promotes the secretion of these inflammatory cytokines.

A group of Univ. Grenoble Alpes discussed how the expression of various CLRs changes in chronic HBV based on experimental results performed using Flow cytometry.
https://onlinelibrary.wiley.com/doi/10.1002/cti2.1208

There are three subclasses of DC: CD1c/BDCA1 (cDC2s), CD141/BDCA3 (cDC1s), and plasmacytoid DCs (pDCs).

Blood cDC2s: DECTIN1, MMR decreased,
Liver cDC2s: DCIR, MMR decreased,
Blood cDC1s: DECTIN1, CLEC9A decreased, Fcɣ Receptor increased slightly,
Liver cDC1s: DCIR, CLEC9A, Fcɣ receptor, MMR decreased, DECTIN1 increased slightly,
Blood pCDs: Little change,
Liver pCDs: DCIR increased, Fcε receptor increased slightly.

Such a change is happening.

Although the changes are very complex, it is worth noting that chronic HBV causes changes in the expression of CLRs in DCs.
Overall, CLR expression seems to be decreasing, which makes it easier for HBV to escape from immune system, right?