Survival times of SARS-CoV-2 and Influenza virus on three types of postcards with different surface coating

A group from Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan, etc. has reported stability of SARS-CoV-2 and Influenza virus on three types of postcards with different surface coating.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590490/

The assessment of the risk of virus transmission through papers, such as postcards, is important. However, the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) on different types of papers is currently unknown.

In this experiment, stability of SARS-CoV-2 and IAV was evaluated on the surface of postcards with three types of coatings, plain paper (PP), inkjet paper (IP), and inkjet photo paper (IPP).
The survival times of SARS-CoV-2 and IAV were significantly shorter on IP and IPP than on PP as shown below (SARS-CoV-2). Therefore, switching from PP to IP or IPP is effective in reducing the viral transmission risks through paper.

Cortical-bone-derived stem cells (mCBSCs) treatments effectively improve myocardial structure and functions after myocardial infarction compared to MSC: Difference in glycosylation

A group from Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Japan, etc. has reported that cortical-bone-derived stem cells (mCBSCs) treatments effectively improve myocardial structure and functions after myocardial infarction compared to MSC.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584423/

Recently, it have been shown that mouse cortical-bone-derived stem cells (mCBSCs) improve cardiac remodeling and functions. The mCBSC-treated hearts showed increased neovascularization, and newly formed cardiac myocytes were also observed. mCBSCs produce a unique combination of immunomodulatory and angiogenic and proangiogenic factors, which may be the reason why mCBSCs were more effective in improving the post-myocardial infarction hearts compared to cardiac-derived stem cells and MSCs.

The self-renewing ability in mCBSCs was higher than that in mMSCs, but the mCBSCs exhibited only chondrogenic differentiation, while the mMSCs exhibited adipogenic, osteogenic, and chondrogenic differentiation. It was also found that mCBSCs secrete a greater amount of TGF-β1 compared to mMSCs, and that the TGF-β1 contributed to the self-migration of mCBSCs and activation of fibroblasts. Migrated CBSCs expressing TGF-β1 may contribute to converting cardiac fibroblasts into myofibroblasts at an infarcted site.

As for cell surface glycans, the relative intensities of three lectins WFA (lacdiNAc), ECA (lactosamine-binding lectin), and MAL-I (α2-3 sialic acid binding lectin) in mCBSCs were higher than those in mMSCs. Moreover, the relative intensities of the three lectins, SNA, SSA, and TJA-I (α2-6 sialic acid binding lectins), in mCBSCs were significantly lower than those in mMSCs. It was considered that this lower expression of α2-6sialic acid may be an indication of specific differentiation towards chondrogenic lineage and not towards adipogenic or osteogenic differentiation.

Previous research has shown that glycans contribute to regulation of the signaling mediated by leukemia inhibitory factor (LIF), Wnt, FGF, bone morphogenetic protein BMP, and Notch, which are required for the maintenance of stem cells. It has been also known that WFA-binding glycans on LIF receptorβ and gp130 regulate LIF/STAT3 signaling, which is required for self-renewal of mouse embryonic stem cells.

In this study, it was found that WFA-binding glycans are more specific to CBSCs than MSCs, and this suggested that WFA-binding glycans may contribute to the self-renewal of CBSCs by regulating LIF/STAT3 signaling, although further studies is required.

Lactobacillus agilis isolated from rhizosphere shows potential as a novel biotherapeutic agent

A group from Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan, etc. has reported that Lactobacillus agilis isolated from rhizosphere of the medicinal plants Ocimum tenuiflorum, Azadirachta indica, Ficus carica shows potential as a novel biotherapeutic agent.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568817/

Potential probiotic bacteria can be used as a biotherapeutic agent and a sustainable alternative to antibiotics, as an anti-oxidative, anti-inflammatory, and anti-diabetic agent without causing any serious side effects. In this experiment, the following assays were performed to select potentials.

Safe status assays
First of all, to exclude potentially harmful bacterial strains, testing of safe status was done before selection of bacterial strains for human as probiotics.
(1) should be negative for blood hemolytic activities and (2) did not show a breakdown of gelatin.

Antibiotic susceptibility
The strains which show less or no resistance to antibiotics were selected, and L. agilis was the best.

In-vitro antibacterial assay
The antibacterial results showed the significant marked antagonistic activity of L. agilis NMCC-15 to kill or inhibit the growth of all the tested bacterial pathogens (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus).

Antioxidant, anti-diabetic, and anti-inflammatory assays
Percentage inhibition of the free radical from the mean values showed the comparable effects of L. agilis supernatant to the standard drug with values 68% and 73%, respectively.
L. agilis inhibited the activities of the α-amylase (anti-diabetic potential) by 51.3% than control.
The supernatant of L. agilis showed 61.6% for denaturation albumin protein while aspirin showed 69% activity.

Two types of multivalent lectins produced from hemagglutinins of clostridium botulinum: Gg binds to Gal/GalNAc and Rn binds to Neu5Ac

A group from Tokyo University of Agriculture and Technology, Tokyo, 183-8509, Japan, etc. has reported two types of multivalent lectins produced from hemagglutinins of clostridium botulinum.
https://www.nature.com/articles/s41598-021-01501-1

Clostridium botulinum is a gram-positive anaerobic bacterium that produces a neurotoxin. Botulinum bacteria are classified into serotypes A to G depending on the antigenicity of the toxin produced. The type C 16S progenitor toxin is composed of a neurotoxin, non-toxic non-hemagglutinin component and several hemagglutinin proteins (HA) designated as HA1, HA2, HA3a and HA3b.

It has been know that type C HA1 has two binding sites: site I and site II. Site I binds to N-acetylneuraminic acid (Neu5Ac), N-acetylgalactosamine (GalNAc) and galactose (Gal) while site II binds to galactose only.

Authors have developed two new multivalent lectins from the above mentioned hemagglutinins of clostridium botulinum designed to have different binding specificities were produced: namely Gg and Rn:
Gg is an Alexa 488 labeled complex with HA1 WADF -HA2 WT-HA3 WT, which binds to Gal/GalNAc,

and, Rn is an Alexa 594 labeled complex with HA1 NQAA-HA2 WT-HA3 WT, which binds to Neu5Ac only.

Antibody response induced by a 3rd boost SARS-CoV-2 vaccination: after 8 months from the 2nd vaccination

A group from The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China, etc. has reported on antibody response induced by a third boost dose of inactivated SARS-CoV-2 vaccine.
https://pubmed.ncbi.nlm.nih.gov/34666622/

In this study, 53 volunteers, who joined in the development and production of inactivated COVID-19 vaccines (it is not sure what company developed the relevant ones, though), received two doses (at 0 and 28 days) of the vaccines in 2020, and they received a 3rd dose 8 months after the 2nd dose recently.

At 0 days, 5 days, 7 days, and 14 days after the 3rd dose, blood was collected from 6 volunteers for the evaluation. It was found that both the anti-S antibody and neutralizing antibody against the original Wuhan strain gradually increased after 5 days, and the positive conversion rate of antibodies reached 100% at 14 days. Interestingly, the memory of IFN-γ-T cells against S, N, M, O antigens of SARS-CoV-2 can be quickly awakened after the 3rd dose.

These results indicate that although the neutralizing antibodies gradually decrease after two doses of inactivated vaccines, the antibody response could be awakened quickly by the 3rd vaccination and the T cell immune memory is still active even after 8 months from the 2nd vaccination.

Development of mannosylated macromolecules specific to each human mannose-binding lectins such as DC-SIGN, Dectin-2, and DEC-205

A group from Department of Chemistry, Massachusetts Institute of Technology, MS, USA, etc. has developed mannosylated macromolecules specific to each human mannose-binding lectins.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549053/

Carbohydrate-binding proteins (lectins) play vital roles in cell recognition and signaling, including pathogen binding and innate immunity. Thus, targeting lectins, especially those on the surface of immune cells, could advance immunology and drug discovery. Lectins are typically oligomeric; therefore, many of the most potent ligands are multivalent. An effective strategy for lectin targeting is to display multiple copies of a single glycan epitope on a polymer backbone; however, a drawback to such multivalent ligands is they cannot distinguish between lectins that share monosaccharide binding selectivity (e.g., mannose-binding lectins such as DC-SIGN, DC-SIGNR, MBL, SP-D, langerin, dectin-2, mincle, and DEC-205) as they often lack molecular precision.

Authors developed β-mannosylated glyco-IEGmers specific to each lectins with mannose binding specificity.

To generate the target mannosylated glycomacromolecules, iterative exponential growth (IEG) cycles beginning from (R)- or (S)-glycidyl propargyl ether (GPE, > 99% ee) were conducted to yield oligo/polytriazoles with precisely 8, 16, or 32 allyl side chains. Macromolecules were produced with three different overall absolute configurations: all (R) (“isotactic”), all (S) (“isotactic”), and alternating (R-alt-S) (“syndiotactic”). To append the mannose residues, these IEGmers were exposed to pure β-thiomannose sodium salt under UV light (λ = 365 nm).

The binding affinity changed from sample to sample over several orders of magnitudes. For example, KA values for DC-SIGN ranged from approximately 1 × 104 for (S)-8mer to about 1 × 108 for (R)-16mer. For dectin-2, it also ranged from ∼1 × 104 to ∼1 × 108. DEC-205 bound all of the glyco-IEGmers with high KA values in the range of ∼1 × 106 to 1 × 109, with the highest KA of all pairwise interactions tested (2.2 × 109).

This wide range in affinity is impressive as the mannose binding epitopes presented was identical among these lectins.

Snake venom (Dimeric PLA2s) from Vipera nikolskii showed high antiviral activity against SARS-CoV-2

A group from Department of Molecular Neuroimmune Signalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia, has reported that Snake venom (Dimeric PLA2) from Vipera nikolskii showed high antiviral activity against SARS-CoV-2.
https://pubmed.ncbi.nlm.nih.gov/34714362/

Two types of Snake venom (Dimeric PLA2) from Vipera nikolskii (HDP-1, HDP-2, and its subunits, HDP-2I and HDP-2P) were evaluated as natural antiviral products.
Complete suppression of the infectivity of SARS-CoV-2 was observed when the viral stock was treated with HDP-2P even at 0.1 µg/ml on Vero E6 cells.
On the other hand, the highest but moderate cytotoxicity was manifested by HDP-2P which at 100 μg/ml reduced cell viability on average by 51%.

These data highlight the potential of PLA2s as a natural product that could prove to be fruitful as the starting point for the development of antiviral drugs.

Saponin treatments could control rhizobacteria

A group from Research Institute for Sustainable Humanosphere, Kyoto University, Japan, etc. has reported that saponin treatments could control rhizobacteria.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538258/

Plant specialized metabolites (PSMs) secreted from roots are called root exudates, and these account for up to 40% of the carbon fixed during photosynthesis. Rhizosphere microbiomes assembled by root exudates promote plant growth and help the host plants overcome biotic and abiotic stresses. However, the association between PSMs and microbiota is not well characterized.
Saponins are a group of PSMs widely distributed in angiosperm plants. They exhibit biological and pharmacological activities, including antibacterial, antifungal, hemolytic, and cytotoxic properties.

Burkholderiaceae, Methylophilaceae, Rhodocyclaceae, Moraxellaceae, Pseudomonadaceae, P3OB-42, Caulobacteraceae, Steroidobacteraceae, Geobacteraceae, and Sphingomonadaceae were enriched in saponin (α-Solanin, dioscin, soyasaponins, and glycyrrhizin) treatments as shown below.

For instance, members of the family Burkholderiaceae are reportedly involved in plant–pathogen suppression via the upregulation of induced systemic resistance-associated genes and the production of sulfurous volatile compounds and siderophores, and members of Sphingomonadaceae have been found to promote plant growth via phytohormone production, alleviation of heavy metal toxicity and drought stress, and pathogen suppression.

Therefore, it is plausible that saponin-producing plants may benefit from attracting those bacterial families to their rhizospheres and roots.

Dual inhibition of TMPRSS2 and Cathepsin B is effective in preventing SARS-CoV-2 infection in ACE2-iPS cells

A group from Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan has reported that dual inhibition of TMPRSS2 and Cathepsin B is effective in preventing SARS-CoV-2 infection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527102/pdf/main.pdf

iPS cells that stably express ACE2 were used for this experiment, and TMPRSS2 and CTSB (Cathepsin B gene) were suppressed to about 1% or less, by using a CRISPER interference system.

It was found that CTSB and TMPRSS2 are required for SARS-CoV-2 to infect ACE2-iPS cells. It is known that TMPRSS2 is present in the cell membrane and CTSB in endosomes, suggesting TMPRSS2 and CTSB play important roles in endocytosis independent and endocytosis-dependent infection, respectively.

From this experiment, it was shown that Double-knockdown of TMPRSS2 and CTSB reduced the viral load to 0.036±0.021%.

WGA lectin could inhibit infection with SARS-CoV-2

A group from Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany, etc. has reported that WGA lectin could inhibit infection with SARS-CoV-2 with an IC50 of <10 ng/mL. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508056/

Vero B4 cells were infected with the SARS-CoV-2PR-1 (Wuhan type) for 1 h and then treated with different concentrations of WGA. Cell culture supernatants were harvested after 3 days and virus production was analyzed via qRT-PCR and Western blot. Treatment with WGA led to a strong reduction of SARS-CoV-2 replication. A concentration of 10 µg/mL WGA completely abolished the presence of viral RNA copies in cell culture supernatants. The inhibitory effect was observed in a dose-dependent manner and was confirmed by Western blot analysis, which revealed an even stronger and dose-responsive reduction of virion production upon treatment with WGA. Collectively, these data provide the first evidence that WGA exhibits antiviral activity against SARS-CoV-2 in Vero B4 cells, with an estimated IC50ub> of <10 ng/mL.

To analyze cytotoxicity of WGA, toxicity assays were performed in VERO B4 and Calu-3 cells. In Vero B4 cells, the TD50 was ≈ 50 µg/mL, resulting in a broad therapeutic window of at least three log stages. These data suggest that WGA could be used to inhibit infection with SARS-CoV-2 in vivo. Let’s expect future clinical studies on this matter.

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