Category: Technology

A group from Fred Hutchinson Cancer Research Center, etc. has investigated the effect of genomic mutations onto two types of monochronal antibodies (LY-CoV555 and LY-CoV016) against RBD of SARS-CoV-2.
https://www.biorxiv.org/content/10.1101/2021.02.17.431683v1

It was found that LY-CoV016 is very weak for K417N mutation, and LY-CoV555 is so weak for E484K mutation. In both cases, IC₅₀ increased more than 1,000 times with these mutations. Therefore, a strategy using antibody cocktails with different monochronal antibodies with different target epitopes would be quite effective in developing therapeutic drugs for rapidly mutating RNA viruses such as SARS-CoV-2.

A group from Massachusetts General Hospital, etc. has reported on effectiveness of two typical vaccines, BNT162b2 (Pfizer) and mRNA-1273 (Moderna), for various SARS-CoV-2 variants occuring in the world.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899476/

Distribution of typical SARS-CoV-2 variants in the world.

Effectiveness of Pfizer and Moderna vaccines is shown by the neutralization response. There seems to be almost no change for B.1.1.7 variant, but the neutralization activity of these vaccines are significantly reduced in B.1.351 v2 and P.1 variants. Two common mutations, K417N and E484K, exist in B.1.351 and P.1 variants, and these mutations do not exist in B.1.1.7. 

A group from Memorial Sloan Kettering Cancer Center, New York etc. has reported on the development of therapeutic agents targeting Galectin-3 for breast and ovarian cancers.
https://www.nature.com/articles/s41598-021-82686-3

In ovarian and breast cancers, mucin named MUC16 with CA125 epitope is highly expressed. Mucins are strongly glycosylated with O-glycans, and the glycan chains are sometimes stretched by adding a poly LacNAc chain to the terminal. Galectin-3 (Gal-3) has affinity to the poly LacNAc, hence Gal-3 could bind to MUC16 via such glycans. Galectin family has various functions, and MUC16 is closely related to cancer cells and is considered to be related to cancer growth and metastasis.

Using a monoclonal antibody (14D11) against Gal-3, the authors evaluated the inhibitory effects of Gal-3 on ovarian and breast cancers in vitro and in vivo. The Kd value for Gal-3 and LacNAc binding was ~0.2mM, and the Kd value for Gal-3 and 14D11 was ~14.6nM. Therefore, it turns out that 14D11 has stronger affinity about 13,000 times.

Two ovarian cancer cell lines (A2780, SKOV3) with high expression of MUC16 were transplanted into mice and the effects of 14D11 administration were compared with survival rates.

In addition, breast cancer cells (MDA-MB-231) were transplanted into mice and the effects of 14D11 administration were compared as below. These experimental results show that inhibition of Gal-3 can reduce cancer growth significantly.

A group from UC Davis had proposed the idea of using ACE2-Fc fusion protein as a therapeutic agent for COVID-19 as follows,
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237295

A group from Chulalongkorn University, Bangkok, Thailand etc. has  developed ACE2-Fc fusion proteins expressed in N. benthamiana leaf, and demonstrated the inhibitory effect of SARS-CoV-2 in vitro. Vero cells were infected with SARS-CoV-2, and then ACE2-Fc fusion protein was applied, 0.84 μg/ml (IC50) was obtained as the inhibitory effect. Why did authors use plants? The advantages of using plants are low cost, scalability of production, and no risks from pathogens of animal or human origin.
https://www.frontiersin.org/articles/10.3389/fpls.2020.604663/full

A group from Univ. of Rochester’s group has developed and used sensor chips with various glycans immobilized on the Arrayed Imaging Reflectometry (AIR) platform as a simple way to detect the hemagglutinin subtypes of influenza viruses and the subtypes of neuraminidase.
https://pubs.acs.org/doi/10.1021/acs.bioconjchem.0c00718

What is more curious is what is the Arrayed Imaging Reflectometry (AIR) platform rather than the application example itself. This platform seemed to be developed in Benjamin Miller Lab., Univ. of Rochester. The principle is physically very simple, growing a thin oxide on a Si substrate with the mirror surface, and using the interference effect of light reflected on the upper and lower surfaces of SiO2 (i.e., at the SiO2/Si interface). There could be a reflection condition that the surface becomes non-reflective as a result of the interference of the diagonally incident light onto the substrate, and molecular interaction between probes pre-fixed on the substrate and applied ligands happens, reflected light appears depending on degree of disruption of the light interference. Therefore, like SPR, AIR does not need fluorescence labeling to the sample (i.e., label-free). The question about this technology would be the sensitivity. However, the above example explained that it provides comparable or better sensitivity than SPR.
https://www.urmc.rochester.edu/labs/benjamin-miller/projects/arrayed-imaging-reflectometry.aspx

A group from Okayama University School of Medicine has reported on a study focusing on glycans and lectins as prognosis markers for IgA nephropathy.
https://www.nature.com/articles/s41598-020-77736-1

They have found excellent prognostic markers from urine as a diagnostic sample with using lectin microarrays for 157 IgA nephropathy patients who received a renal biopsy from 2010 to 2017 at Okayama University Hospital.
The prognosis outcome were based on a decrease in glomerular filter rate (eGFR) (> 4 mL/min/1.73 m2/year), or eGFR ≥ 30% decline from baseline. T Score was used for the statistical evaluation, and  it was found that ECA lectins (with glycan binding specificity to Galβ1-4GlcNAc) and NPA lectins (with glycan binding specificity to High Mannose) could be good prognostic markers.
ECA:(odds ratio[OR] 2.84, 95% confidence interval[CI] 1.11–7.28)
NPA:(OR 2.32, 95% CI 1.11–4.85)
T Score is calculated by multiplying the standardized percentile rank by 10 and adding 50. T0, T1, T2 indicate Oxford classification about tubular atrophy and interstitial fibrosis.

A group from the Center for Child Health and Development described a regenerative medicine approach to thin endometrium (endometrial stunting), which is one of causes of infertility.
https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02188-x

There are various causes of infertility, but one of them is a thin endometrium (endometrial stunting). It is known that thin endometrium make ovoimplantation difficult, but little is known about the reason. Treatments for endometrial stunting include (1)estradiol replacement, mineral and vitamin administration, and from regenerative medicine approaches, (2) administration of platelet-rich plasma, (3) menstruation-derived stem cells, and (4) use of autologous transplantation of exogenously prepared endometrium cell sheets.

In a regenerative medicine approach, however, it would be very important how efficiently to culture the endometrium under xeno-free conditions. The endometrium is basically difficult to culture with feeder-free, and from the view point of xeno-free, the authors have developed a method of using autologous endometrial stromal cells as a feeder  instead of MEF. They also used special media (ESTEM-HE) in terms of accelerating endometrial cell growth. In the figure below, continental medium is DMEM and epithelium-specific medium is a special medium named ESTEM-HE.

A group from Grossman School of Medicine, New York has reported on the efficacy of Pfizer’s current new coronavirus (COVDI-19) vaccine for B.1.1.7 (UK lineage variant) and B.1.351 (South African lineage variant).
https://www.biorxiv.org/content/10.1101/2021.02.05.430003v1

This blog site also contains a similar research result from other research groups (see article on February 6, 2021).
The Group’s reporting has a similar trend. The current Pfizer vaccine is not so affected by UK variant, but it seems certain that its effectiveness is likely to be significantly lower for South African variant.

RT-PCR is the Gold Standard for the detection of the new coronavirus (SARS-CoV-2).
A group from Mahidol University, Nakhon Pathom, Thailand etc. has reported an electrochemical detection method that has the same sensitivity and specificity as RT-PCR and do not require expensive devices.
https://www.nature.com/articles/s41467-021-21121-7

In order to detect SARS-CoV-2 with high sensitivity, of course, a gene amplification process is required. They adopted Rolling Circle Amplification (RCA). The RCA method, like the PCR and LAMP methods, has the advantage that carryover contamination has a small impact on the next amplification process and can be amplified in an isothermal bath at around room temperature (25°C to 37°C). The RCA amplicon (Padlock probe) was designed as shown below and was consist of Target gene specific to the target you want to detect (N-gene, S-gene, etc. of SARS-CoV-2), Universal capture probe-binding region, and Generic reporter probe-binding region. With this Padlock probe, RCA results in long DNA amplicons containing hundreds of tandem repeats of the Padlock DNA complementary sequence. For this RCA products, hybridize probe-conjugated magnetic bead particle (CP-MNB) and Silica methylene blue reporter probe (SiMB-RP) to obtain the final product. Methylene blue or Acridine orange was used to as a redox regent. The current obtained by the electrochemical reaction increased with copy numbers as shown below. As a result, the detection limit sensitivity reached 1 copy/uL.

A group from University of Helsinki etc. has reported on the relationship between Vitamin C and COVID-19.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848027/

In healthy people, a Vitamin C intake of about 0.1 g/day is enough to maintain the concentration of Vitamin C in the blood. However, when infected with COVID-19 and becomes severe, the concentration of Vitamin C in the blood decreases sharply, and it can be reduced to the same level as vitamin C deficiency and further to a level that is almost undetected.

Taking a large amount of Vitamin C (6-8 g/day) has the following effects:
Reduced ICU treatment duration by an average of 8%
Reduced fatality from 35% to 78%

Since there are no side effects of Vitamin C, this is also considered to be effective for the COVID-19 treatment.