Archive 21/1/16

Screening plant-derived inhibitors targeting SARS-CoV-2 precursor protein main protease ( Mpro)

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 (Mpro) 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.

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

Name Energy (kcal/mol) Predicted LD50 mg/kg
Gallic acid − 17.45 2260
Quercetin − 15.81 159
Naringin − 14.50 2300
Capsaicin − 13.90  47
Psychotrine − 13.50 480


Presence of neutral antibodies against all β-coronaviruses

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.

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.

BanLec (a kind of Lectin) shows potential as an antiviral reagent against the new coronavirus (SARS-CoV-2)

It has already been shown that the new coronavirus (SARS-CoV-2) has 22 N-type glycan modification sites (see, for example,

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.

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.

Neutralising antibody response of the new coronavirus (SARS-CoV-2): RNA mutations in viral populations occur during treatment

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.

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.)

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.

Limited effect of glycans on the binding of the new coronavirus (SARS-CoV-2) and ACE2

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 .

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.

Systemic corticosteroids are better than Tocilizumab (Actemula) in the treatment of the new coronavirus (COVID-19)

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.

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.

The prognostic symptoms of the new coronavirus (COVID-19) last more than 40 days

A group of University College London has reported on the prognostic symptoms of the new coronavirus (COVID-19).

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)

Ct-value of RT-PCR in the new coronavirus (SARS-CoV-2)

A group of Albert Einstein College of Medicine has reported on the correlation between Ct-values and hospital mortality in RT-PCR for the new coronavirus (SARS-CoV-2) from a retrospective statistical analysis.

This is the result of a retrospective study on 1,044 patients hospitalized with COVID-19.
The Ct-value of RT-PCR is divided into quartiles for statistical analysis.
Q1:     Ct =<22.9
Q2: 23.0 <Ct <27.3
Q3: 27.4 <Ct <32.8
Q4: Ct=>32.9

As a result, it has been shown that hospital mortality and Ct-values are inversely correlated.
In other words, the lower the Ct-value, the higher the hospital mortality, and the higher the Ct-value, the lower the hospital mortality.

So, it turns out that the higher the amount of exposed viruses or the proliferation, the higher the hospital mortality.

Diagnosis and prognosis of the new coronavirus (COVID-19) from urine color and foaming

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.

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.

Powered by WordPress |Copyright © 2020 Emukk. All rights reserved