SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

Memory T Cells Discrepancies in COVID-19 Patients.

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4+ and CD8+ memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8+ T cells and effector memory-expressing CD45RA CD8+ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4+ T cells, CD8+ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8+ TSCMs and CD4+ TNs cells, while female patients had a significantly higher percentage of effector CD8+CD45RA+ T cells. Moreover, altered percentages of CD8+ TNs and memory CD8+CD45RO+ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.

Phenotypical changes of hematopoietic stem and progenitor cells in COVID-19 patients: Correlation with disease status.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19.

Effects of microbial biostimulants (Trichoderma album and Bacillus megaterium) on growth, quality attributes, and yield of onion under field conditions.

Microbial biostimulants (MBs) promote plant growth and stress tolerance in a sustainable manner. However, precise field trials of MBs are required in natural setting with a range of crop varieties to harness the benefits of biostimulants on crop yield improvement. This study investigated the effects of two MBs, Trichoderma album and Bacillus megaterium, on an onion cultivar's growth, nutritional qualities, antioxidant properties, and yield potentials under field conditions for two successive years. Before transplantation, onion bulbs were gelatin-coated with 2.0 and 4.0 g L-1 of each of the MB. Results revealed that MBs-pretreated onion plants exhibited better growth indices, photosynthetic pigment contents, and yield-attributing features like bulb weight than control plants. Nutraceutical analysis demonstrated that T. album-pretreated (by 2.0 g L-1) onion cultivar enhanced the level of K+ (by 105.79%), Ca2+ (by 37.77%), proline (by 34.21%), and total free amino acids (by 144.58%) in bulb tissues over the control plants. Intriguingly, the pretreatment with both T. album and B. megaterium (by 2.0 g L-1) increased the levels of total soluble carbohydrates (by 19.10 and 84.02%), as well as antioxidant properties, including increased activities of superoxide dismutase (by 58.52 and 31.34%), catalase (by 164.71 and 232%), ascorbate peroxidase (by 175.35 and 212.69%), and glutathione-S-transferase (by 31.99 and 9.34%) and improved the contents of ascorbic acid (by 19.1 and 44.05%), glutathione (by 6.22 and 33.82%), and total flavonoids (by 171.98 and 56.24%, respectively) in the bulb tissues than control plants. Although both MBs promoted the growth and nutraceutical qualities of onion bulbs, T. album pretreatment showed better effects than that of B. megaterium in the field settings. Based on the morphophysiological attributes and biochemical properties, a low dose (2.0 g L-1) was more effective than a high dose (4.0 g L-1) of T. album in promoting onion growth. Overall, the current research findings imply that T. album might be a potential MB in improving growth and quality attributes, and hence the productivity of onion cultivars under field circumstances.

Human Wharton's Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses.

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton's jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.

Antioxidants and Bioactive Compounds in Licorice Root Extract Potentially Contribute to Improving Growth, Bulb Quality and Yield of Onion (Allium cepa).

The increasing culinary use of onion (Alium cepa) raises pressure on the current production rate, demanding sustainable approaches for increasing its productivity worldwide. Here, we aimed to investigate the beneficial effects of licorice (Glycyrrhiza glabra) root extract (LRE) in improving growth, yield, nutritional status, and antioxidant properties of two high-yielding onion cultivars, Shandaweel and Giza 20, growing under field conditions in two consecutive years. Our results revealed that pretreatments of both onion cultivars with LRE exhibited improved growth indices (plant height and number of leaves) and yield-related features (bulb length, bulb diameter, and bulb weight) in comparison with the corresponding LRE-devoid control plants. Pretreatments with LRE also improved the nutritional and antioxidant properties of bulbs of both cultivars, which was linked to improved mineral (e.g., K+ and Ca2+) acquisition, and heightened activities of enzymatic antioxidants (e.g., superoxide dismutase, catalase, ascorbate peroxidase, glutathione peroxidase, and glutathione S-transferase) and increased levels of non-enzymatic antioxidants (e.g., ascorbic acid, reduced glutathione, phenolics, and flavonoids). LRE also elevated the contents of proline, total free amino acids, total soluble carbohydrates, and water-soluble proteins in both onion bulbs. In general, both cultivars displayed positive responses to LRE pretreatments; however, the Shandaweel cultivar performed better than the Giza 20 cultivar in terms of yield and, to some extent, bulb quality. Collectively, our findings suggest that the application of LRE as biostimulant might be an effective strategy to enhance bulb quality and ultimately the productivity of onion cultivars under field conditions.

The phyto-impact of fluazinam fungicide on cellular structure, agro-physiological, and yield traits of pepper and eggplant crops.

Fluazinam is a widely used fungicide; most of the available information associated with its impact predominately on birds, invertebrates, mammals, and algae and scarce works studied its impact on crop plants. A two years-field experiments were conducted to study the response of pepper and eggplant to fluazinam at 0, 1, 2, and 3 times of the fluazinam-recommended dose (0, 0.5, 1, and 1.5 mL/L). The results revealed that fluazinam did not cause toxic effect on the tested plants except for temporary decline of shoot weights and lengths after 3 days of fluazinam application. However, fluazinam improved the physiological status of leaves via promoting metabolites, antioxidants, better membrane integrity, and adjustment of the redox status of fluazinam-sprayed plants. The ultrastructure changes of fluazinam-treated leaves associated with increment of chloroplasts' starch granules, giant nucleus, and elevated number of mitochondria. After 35 days of treatments, plant length of fungicide-treated plants was found to be higher than control and flowering time showed significant earliness. Furthermore, the yield traits were increased significantly in response to fluazinam. Our findings suggested that fluazinam-treated plants could initiate an early defense mechanism to mitigate the permanent growth retardation. This study could serve as a matrix for further studies to seek elucidation of plants' response to other doses of fluazinam. Graphical abstract .