Mx

A group from School of Medicine, Keio Univ. has reported a cohort study on antibody responses in asymptomatic to mild new coronavirus (COVID-19) patients who were positive for PCR testing in Japan.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787511/

Many overseas cohort studies have targeted patients with more symptomatic and severe cases, and antibody responses have appeared in 80% to 100% of patients three weeks after infection. Numerous studies have also shown that these antibodies correlate with age, severity, lymphopenia, and serum CRP levels.

This cohort study was conducted in asymptomatic to milder patients than in known cohort studies, and 87.5% of asymptomatic patients and 23.5% of mild patients did not have antibody responses.

A group of Fondazione IRCCS Estituto Neurologico Carlo Besta, Via Padova, Milan, Italy etc. believes that the low efficacy of antiviral drugs such as cytokine inhibitors is (1) probably due to delays in administration in which the virus causes an inflammatory response and is no longer the main protagonist, (2) the relatively low efficacy of cytokine inhibitors is explained because they only act on one or a few of the dozens of cytokines, and (3) other inflammatory mediators (reactive oxygen and nitrogen species) are not targeted.

When inflammatory mediators are over-generated, reactive species cause extensive cell and tissue damages. The only drug known to inhibit the over production of active species and cytokines is methylene blue, a low-cost dye with antiseptic properties that is effectively used in the treatment of malaria, urinary tract infections, septic shock, and methaemoglobinaemia. They suggest testing methylene blue to treat COVID-19 acute respiratory distress syndrome.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728423/

The virus envelope of the new coronavirus (SARS-CoV-2) contains S proteins, E proteins, and M proteins. Because S proteins are so deeply involved in the infection, so much research has been done targeting S proteins. However, very little information is available on the structure and function of M proteins. In general, the function of the M protein is understood as the protection of the viral particle structure, and it is thought that the RNA-N protein complex and the S-protein bind to the M protein, bud out as infectious particles in the small cavity, and are released out of the cell by exocytosis.

A group of King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia focused on M proteins and its differences between SARS-CoV-2, SARS-CoV, and MERS-CoV.
https://www.sciencedirect.com/science/article/pii/S1018364720304493?via%3Dihub

The following points are pointed out:

The M protein is a transmembrane protein, and there are N-terminal domain and C-terminal domain on either side of the three transmembrane domains.
From the viewpoint of the amino acid sequence, SARS-CoV-2 has an S4 residue (221-224) inserted, and it would be an unique feature of SARS-CoV-2.
As intrinsically disordered regions, there are two regions (1-7, 205-222) in SRAS-CoV-2, three regions (1-6, 207-210, 216-221) in SARS-CoV, and two regions (1-6, 216-219) in MERS-CoV, and these differences would reflect viral particles protection capability in different environments of the virus and might be related to viral transmission mode.
Domains that could be potential B-cell epitopes would be:
SARS-CoV2    183-189 ASQRVAG, 200-217 RIGNYKLNTDHSSSSDNI
SARS-CoV     183-188 SQRVGT, 199-215 RIGNYKLNTDHAGSNDN
MERS-CoV     180-188 MVKRQSYGT, 200-211 AGNYRSPPITAD

Similar to the last blog, a group of Ladake Akintola Unyv. of Technology, Ogbomoso, Oyo State Nigeria has evaluated the inhibitory effects of saponins and tannins by molecular docking and molecular dynamics simulations, targeting SARS-CoV-2 precursor protein main protease (M^pro).
https://link.springer.com/article/10.1007/s40203-020-00071-w

Saponins are found in plant roots, leaves, stems, etc., but are especially found in beans and are known to have antioxidant properties. On the other hand, tannins are astringent components contained in many seeds, and astringency of persimmons is a good example of tannin. Tannins strongly bind to proteins and have the effect of causing denaturation, and the effect of tannins on their properties is called “Astringent.”

The results are as follows, but may show potential antiviral effects that are no less so than remdesivir. Evaluation in vivo is expected.

When the new coronavirus (SARS-CoV-2) infects host cells, a huge precursor protein is synthesized from RNA derived from the virus. The precursor protein is cleaved by various proteases and becomes functional proteins necessary for the growth of viruses. The main protease (M^pro) is one of the such precursor proteases and is an essential one for the growth of viruses.

A group of Univ. of Medical Sciences and Technology, Khartoum, Sudan has used this main protease to evaluate the inhibitory effects of plant-derived components used as traditional Sudanese medicines by molecular docking and molecular dynamic simulations.
https://link.springer.com/article/10.1007/s40203-020-00073-8

As a result, the following plant-_derived ingredients are expected as inhibitors of the novel coronavirus. Expect in vivo ratings.

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.