Impacts of SARS-CoV-2 Omicron variant on Infectivity, Vaccine breakthrough, and Antibody resistance

A group from Department of Mathematics, Michigan State University, MI, USA, etc. has reported on Infectivity, vaccine breakthrough, and antibody resistance of SARS-CoV-12 Omicron variant.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647651/

Infectivity:
The Infectivity of SARS-CoV-2 is mainly determined by the binding affinity of the ACE2 and RBD complex, although the furin cleavage site plays a crucial role as well. Omicron has three mutations at the furin cleavage site and 15 mutations on the RBD, suggesting a significant change in its infectivity. Changes in the infectivity of Omicron were analyzed by examining the Binding free energy (BFE) changes of the ACE2 and S protein complex induced by 15 Omicron RBD mutations. As a result, Omicron is to be about 2.8 times as infectious as the Delta (i.e., BFE change: 1.57kcal/mol).

Vaccine breakthrough:
A molecule-based data-driven analysis as done about Omicron’s impact on vaccines through a library of 132 known antibody and S protein complexes. Changes in the binding free energy induced by 15 RBD mutations on these complexes were evaluated to understand the potential impact of Omicron’s RBD mutations to vaccines. This study does not include a few known antibody-S protein complexes that are far away from the RBD, such as those in the N-terminal domain (NTD), due to limited experimental data in the antibody library. As a result, Omicron’s vaccine-escape capability will be about twice as high as that of the Delta variant.

Antibody resistance:
Omicron will have a very mild negative impact on the Regeneron cocktail.

Glycan profile of Schistoeoma mansoni EVs and those origins: Importance of α-6 Sialic acids

A group from Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, QC, Canada, etc. has reported on glycan profile of Schistoeoma mansoni EVs and those origins.
https://www.mdpi.com/2076-0817/10/11/1401/htm

Using lectin microarrays, it was identified several lectins that exhibit strong adhesion to Schistosoma mansoni EVs, suggesting the presence of multiple glycan structures on these vesicles. Interestingly, SNA-I, a lectin that recognises structures with terminal α2-6 sialic acid, displayed strong affinity for S. mansoni EVs. SNA-II and RCA-I, which have affinity for structures which are frequently terminated with sialic acids showed strong intensities as well. In addition, the four mannose-binding lectins, Calsepa, NPA, GNA and HHA, showed strong intensities, suggesting abundance of high-mannose glycans.

Question is the origin of sialic acid.
To identify worm structure(s) as possible sources of EVs, we performed histochemistry on whole adult worms with three lectins that exhibited strong affinity for S. mansoni EVs (DSA, RCA-I and SNA-I). 100% of tegumental cells are positive for SNA-I labelling, DSA labels definitive tegumental cells and the gut of the parasite, and RCA-I labelled various structures within the worm, including potential tegumental cells and what appear to be the excretory pore and excretory tubules. Together, these results may indicate the presence of multiple EV sub-populations and the involvement of the tegument and the digestive and protonephridial (excretory) systems in the release of EVs from adult schistosomes.

This finding on glycosylation profile of Schistosoma mansoni EVs and those origins is of interest, as sialic acids play important roles in the context of infection by aiding immune evasion, affecting target recognition, cell entry, etc.

Titanium (Ti) foliar application promotes plant growth by Phosphorus (P) uptake through in root auxin content and photosynthetic efficiency

A group from College of Agronomy, Sichuan Agricultural University, Chengdu, China, etc. has reported that Titanium (Ti) foliar application increases Phosphorus (P) uptake through in root auxin content and photosynthetic efficiency.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631872/

Under normal light (NL), photosynthetic Rate increased significantly in response to T2 (14.06%) and T3 (30.46%) against T0 (control) in High P condition, whereas in Low P condition, a significant increase was recorded in T2 (21.98%), T3 (38.81%), and T4 (21.43%) as compared to control, where T0, T1, T2, T3 and T4 mean different concentrations of Ti (T0 = 0, T1 = 125, T2 = 250, T3 = 500 and T4 = 1,000 mg/L), and high P (HP) = 100 mg/kg and low P (LP) = 10 mg/kg.

It was found that the increase in root growth traits such as root hairs, root length, lateral root formation and root surface area was associated with root auxin content. This increase in the morphological characteristics of roots due to the Auxin content significantly improved the efficiency of nutrient absorption, for example P.

Effect of Ti application on (A) root length, (B) root surface area, (C) root volume, and (D) root diameter of soybean under NL and shade (SC) combined with Low P and High P conditions.

Lipid nanoparticle (LNP) enhances the efficacy of mRNA vaccines as a versatile adjuvant

A group from Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA has shown that Lipid nanoparticle (LNP) enhances the efficacy of vaccines as a versatile adjuvant using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566475/

Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. LNP-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized.

To demonstrate that this LNP formulation can provide adjuvant activity for other antigens, empty LNP (eLNP)- and AddaVax-adjuvanted SARS-CoV-2 spike protein subunit vaccines were evaluated using mice. Mice were immunized with a single dose of recombinant SARS-CoV-2 spike protein receptor binding domain (rRBD) adjuvanted with eLNP or AddaVax. As a positive control, another group of mice was immunized with nucleoside-modified RBD mRNA-LNP. It was found that LNP-adjuvanted vaccines elicited durable RBD-specific IgG titers that were significantly higher than the AddaVax-elicited responses.

To evaluate the adjuvant properties of LNPs with and without the ionizable lipid, mice were immunized with hemagglutinin recombinant protein (rHA) mixed with the two different formats of eLNP. The eLNP with the ionizable lipid showed high hemagglutinin inhibition titers, however, strikingly, eLNP not containing the ionizable lipid did not possess adjuvant activity.

IL-6 has been shown to be an early regulator of T follicular helper (Tfh) cell differentiation. Tfh cells are a subset of CD4+ T cells specialized in regulating affinity maturation of B cells in germinal centers (GCs). Induction of Tfh cells is critical for durable, protective Ab responses. It was found that the eLNP containing the ionizable lipid (eLNP) and mRNA-LNP induced large amounts of proinflammatory cytokines and chemokines, whereas the LNP lacking the ionizable lipid and AddaVax elicited lower cytokine and chemokine concentrations.

where, empty LNP (eLNP), AddaVax (an MF59-like adjuvant).

Effects of flooding on spring wheat rhizosphere

A group from Microbial Biogeochemistry, Research Area Landscape Functioning, Leibniz Center for Agricultural Landscape Research e.V., Müncheberg, Germany, etc. has reported effects of flooding on spring wheat rhizosphere.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602104/

Flooding caused followings,
(i) significant increase of bacterial taxa with anaerobic respiratory capabilities, such as members of Firmicutes and Desulfobacterota,
(ii) a significant reduction in Actinobacteria and Proteobacteria,
(iii) depletion of several putative plant-beneficial taxa, and
(iv) increases of the abundance of potential detrimental bacteria.

To be more specific, flooding promoted an enrichment of the genera Geobacter and Clostridium. It is known that several Clostridium species might cause soft rot disease in several vegetable crops and their abundance significantly increased with heavy rainfall and flooding. On the other hand, a dramatic reduction of the abundance of Streptomyces and Spinghomonas occurred in all flooding samples, which have been described as beneficial for wheat growth. Members of these two genera, are able to solubilize inorganic phosphorus, to form siderophores and affect phytohormones production and might be involved in biocontrol activity.

Bacteria affiliated to the genus Saccharimonadia, which shows putative beneficial features such as improving nitrogen uptake efficiency and promoting nutrient conversion, were mainly depleted in flooded roots. A similar trend was observed in the rhizosphere for families Rhizobiaceae and Xanthobacteraceae.

Members of different Massilia species are considered as putatively plant-beneficial (in terms of producing proteases, sidephores and the auxin indole-3-acetic acid). Massilia ASVs were significantly more abundant in the control roots of young plants, but they were not detected in those of the flooded ones. Likewise, the flooded wheat roots at booting stage revealed a significant reduction of Flavobacterium ASVs, which are known for plant growth promoting traits. Bacteria of this genus have the capabilities to solubilize phosphate, use of 1-amino cyclopropan-1-carboxylate as sole nitrogen source and production of auxin, siderophores, salicylic acid, antifungal chitinases and hydrogen cyanide.

In summary, these findings demonstrated that flooding significantly altered negatively the assemblage dynamics of the root microbiota, with a significant depletion of putatively beneficial bacterial taxa associated with the root and rhizosphere of spring wheat plant.

Relationship between SARS-CoV-2 mutations and those related concerns

A group from University of Florida College of Medicine, Gainesville, FL, USA, has summarized relationship between SAS-CoV-2 mutations and those related concerns.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606318/

Mutations in the RBD
RBD mutations (such as K417 N, L452R, E484K) have the potential to influence neutralizing antibody binding. One RBD mutation, N501Y, was shown to increase the affinity of the spike protein for the host receptor ACE2. These advantageous mutations acquired in the spike protein S1 NTD and RBD possibly enhance receptor/co-receptor binding.

Mutations in the NTD
Although it is clear why mutations in the RBD have the potential to change virus fitness (by altering neutralizing antibody and host cell ACE2 binding), it is not clear why advantageous distinguishing mutations are emerging in the NTD. Since SARS-CoV-2 elicits neutralizing antibodies that bind multiple epitopes on the spike protein, including the NTD, it is very much likely that the NTD participates in an important but unknown function related to virus fitness (e.g., co-receptor binding).

Mutations at interchain contacts in the spike protein trimer
A570D, D614G, A701V, D950 N, and S982A are located at interchain contact sites. The substitutions at spike trimer interfaces likely reduce intermolecular binding affinity. These acquired mutations likely destabilize the spike protein in a manner that enhances dynamic virus processes including spike protein cleavage, structural rearrangement and host cell fusion mechanisms.

Mutations in the furin cleavage site
Mutations in position 681 of the spike protein can be seen in the highly transmissible alpha and delta variants, but not less transmissible variants of concern, beta and gamma. Position 681 is located adjacent to the RRAR proprotein convertase motif (furin cleavage site) considered a hallmark of high pathogenesis. Since endosomal S1/S2 cleavage occurs in an acidified environment, positively charged amino acids at position 681 in highly transmissible variants (H in alpha, R in delta) have the potential to influence the rate of spike protein cleavage and subsequent membrane fusion mechanisms to gain cell entry.

ACE2 and BSG/CD147 are involved in SARS-CoV-2 infection of human iPS cell-derived podocytes

A group from Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA, etc. has reported that ACE2 and BSG/CD147 are involved in SARS-CoV-2 infection of human iPS cell-derived podocytes.
https://pubmed.ncbi.nlm.nih.gov/34816259/

Human iPS cell-derived podocytes express many host factor genes (including ACE2, BSG/CD147, TMPRSS2, CTSL, CD33, DC-SIGN/CD209, SIGLEC9, SIGLEC10, ACTR3, CLEC10A) associated with SARS-CoV-2 binding and viral processing. It is known that proteases such as Transmembrane Serine Protease 2 (TMPRSS2) or cathepsin L (CTSL) promote fusion and internalization of the receptorviral spike complex. Human iPS cell-derived podocytes expressed lower levels of ACE2 and TMPRSS2 when compared to Calu-3, and both BSG/CD147 and CTSL were expressed at high levels as shown below.

Nevertheless, podocytes derived from human iPS cells were directly infected with SARS-CoV-2 at low Multiplicity of Infection (MOIs) of 0.01 to 1, and intriguingly, there was significantly more viral uptake in the podocytes than Calu3 (p-value < 0.0001) and Caco-2 cells (p-value < 0.0001). Pre-treatment of infected podocytes with both anti-ACE2 and anti-BSG/CD147 antibodies at a concentration as low as 0.1 µg/ml significantly diminished viral uptake (p-value < 0.0001), suggesting that both ACE2 and BSG/CD147 are involved in SARS-CoV2 internalization in human iPS cell-derived podocytes.

Plants detoxify Tetrabromobisphenol A (TBBPA) by glycosylation, but rhizobacteria deglycosylate it again.

A group from Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China, etc. has reported that plants detoxify Tetrabromobisphenol A (TBBPA) by glycosylation, but rhizobacteria deglycosylate it again.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603600/

TBBPA is among the most commonly used brominated flame retardants owing to its excellent properties and low price, and its annual application is continually increasing.
Plants can absorb TBBPA from water, soil, and air. Plants can transform various organic contaminants. The biotransformation of organic compounds in plants can be categorized into phase I, II, and III reactions according to the green liver concept of phytoremediation. For phenolic compounds that contain active hydroxyl groups, glycosylation is an important and common phase II reaction.

Glycosylated metabolites are generally more water soluble than parent contaminants and are therefore easily excreted from plant roots to the outside solutions. Some studies have reported that glycosylated metabolites can also be bound to cell walls and/or compartmentalized in special cell organelles, such as vacuoles. Thus, the formation of glycosylated metabolites can prevent contaminants from accumulation and translocation within plants, and they can decrease the toxic effects of the contaminants on plants.

In this work, the formation of glycosylated metabolites of TBBPA in pumpkin plants and their subsequent excretion from roots to hydroponic solutions effectively decreased the accumulation of TBBPA in plants. However, the deglycosylation of glycosylated metabolites mediated by the microorganisms back to their parent TBBPA revealed more complex uptake and biotransformation processes in these plant–microorganism systems. The TBBPA produced from the observed deglycosylation process can be then absorbed and cause adverse effects on plants and other soil organisms again.

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.

Fungal cell wall polysaccharides β-(1, 3)-glucan and α-(1, 3)-glucan activate the Wnt/β-catenin pathway in human DCs.

A group from Institut National de la Santé et de la Recherche Médicale, Centre de Recherché des Cordeliers, Sorbonne Université, Université de Paris, France, etc. has reported that C-type lectins are necessary in induction of the Wnt/β-catenin pathway and fungal cell wall polysaccharides β-(1, 3)-glucan and α-(1, 3)-glucan, but not chitin, activate the Wnt/β-catenin pathway in human DCs.
https://journals.asm.org/doi/10.1128/mBio.02824-21

Aspergillus fumigatus is an omnipresent airborne fungal pathogen. Although inhaled conidia are usually eliminated in healthy individuals, they may cause hypersensitization, severe asthma with fungal sensitization, allergic bronchopulmonary aspergillosis, colonization of altered respiratory epithelium, and aspergilloma in existing pulmonary lesions.

Innate immune cells, including macrophages, dendritic cells (DCs), and neutrophils, are involved in antifungal activity against A. fumigatus. Upon fungal encounter, DCs engage their various pattern recognition receptors (PRRs) to recognize the evading pathogen. These A. fumigatus-educated DCs subsequently instruct distinct CD4+ T-cell polarization like Th1, Th2, Th17, and FoxP3+ regulatory T cells (Tregs). Among these, Th2 and Th17 responses are nonprotective for Aspergillus infection. On the other hand, Th1 cells have a major role for the induction of protective immune responses. Although Tregs are immunosuppressive and promote chronic and persistent infection, they are also critical for preventing inflammation-associated tissue damage. Therefore, the balance between Th1 and Treg responses is critical for the protective immune response against A. fumigatus.

Recent studies have demonstrated the involvement of Wnt/β-catenin pathway for the induction of tolerogenic functions in DCs and promotion of Treg responses via various anti-inflammatory mechanisms, like expression of IL-10, transforming growth factor beta (TGF-β), and retinoic acid.

By using A. fumigatus as a model, it was shown that fungal species activate the Wnt/β-catenin pathway in human DCs, along with the secretion of Wnt ligands Wnt1 and Wnt7a. Inhibition of the Wnt pathway resulted in decreased DC maturation and selective inhibition of anti-inflammatory cytokine IL-10 without affecting the secretion of most of the proinflammatory cytokines. Abrogation of the Wnt/β-catenin pathway in DCs also led to reduced Treg polarization without altering the polarization of other CD4+ T-cell subsets.

It was also found that C-type lectins are involved in induction of the β-catenin pathway and A. fumigatus’s cell wall polysaccharides β-(1, 3)-glucan and α-(1, 3)-glucan, but not chitin, activate the β-catenin pathway in human DCs.

where, CA=unstimulated, SC=stimulated with swollen conidia