Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of ...coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.
Background In pandemic COVID-19 (coronavirus disease 2019), the prognosis of patients has been determined using clinical data and CT (computed tomography) scans, but it is still unclear whether chest ...CT characteristics are correlated to COVID-19 severity. Aim To explore the potential association between clinical data and 25-point CT score and investigate their predictive significance in COVID-19-positive patients at Fayoum University Hospital in Egypt. Methods This study was conducted on 252 Egyptian COVID-19 patients at Fayoum University Hospital in Egypt. The patients were classified into two groups: a mild group (174 patients) and a severe group (78 patients). The results of clinical laboratory data, and CT scans of severe and mild patients, were collected, analyzed, and compared. Results The severe group show high significance levels of CRP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, ferritin, lactate dehydrogenase (LDH), neutrophil percent, and heart rate (HR) than the mild group. Lymphopenia, hypoalbuminemia, hypocalcemia, and decreased oxygen saturation (SpO2) were the most observed abnormalities in severe COVID-19 patients. Lymphopenia, low SpO2 and albumin levels, elevated serum LDH, ferritin, urea, and CRP levels were found to be significantly correlated with severity CT score (P<0.0001). Conclusion The clinical severity of COVID-19 and the CT score are highly correlated. Our findings indicate that the CT scoring system can help to predict COVID-19 disease outcomes and has a strong correlation with clinical laboratory testing.
Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome ...(ARDS).
To describe the clinical characteristics of patients with ARDS-COVID-19.
This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP), thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH).
The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19.
COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.
Expansion of COVID-19 worldwide increases interest in unraveling genomic variations of novel SARS-CoV-2 virus. Metadata of 408,493 SARS-CoV-2 genomes submitted to GISAID database were analyzed with ...respect to genomic clades and their geographic, age, and gender distributions. Of the currently known SARS-CoV-2 clades, clade GR was the most prevalent worldwide followed by GV then GH. Chronological analysis revealed expansion in SARS-CoV-2 clades carrying D614G mutations with the predominance of the newest clade, GV, in the last three months. D614G clades prevail in countries with more COVID-19 cases. Of them, the clades GH and GR were more frequently recovered from severe or deceased COVID-19 cases. In contrast, G and GV clades showed a significantly higher prevalence among asymptomatic patients or those with mild disease. Metadata analysis showed higher (p < 0.05) prevalence of severe/deceased cases among males than females and predominance of GR clade in female patients. Furthermore, severe disease/death was more prevalent (p < 0.05) in elderly than in adults/children. Higher prevalence of the GV clade in children compared to other age groups was also evident. These findings uniquely provide a statistical evidence on the adaptation-driven evolution of SARS-CoV-2 leading to altered infectivity, virulence, and mortality.
The aim of this study is to characterize the antimicrobial resistance of Campylobacter jejuni recovered from diarrheal patients in Belgium, focusing on the genetic diversity of resistant strains and ...underlying molecular mechanisms of resistance among Campylobacter jejuni resistant strains isolated from diarrheal patients in Belgium. Susceptibility profile of 199 clinical C. jejuni isolates was determined by minimum inhibitory concentrations against six commonly-used antibiotics (ciprofloxacin, nalidixic acid, tetracycline, streptomycin, gentamicin, and erythromycin). High rates of resistance were observed against nalidixic acid (56.3%), ciprofloxacin (55.8%) and tetracycline (49.7%); these rates were similar to those obtained from different national reports in broilers intended for human consumption. Alternatively, lower resistance rates to streptomycin (4.5%) and erythromycin (2%), and absolute sensitivity to gentamicin were observed. C. jejuni isolates resistant to tetracycline or quinolones (ciprofloxacin and/or nalidixic acid) were screened for the presence of the tetO gene and the C257T mutation in the quinolone resistance determining region (QRDR) of the gyrase gene gyrA, respectively. Interestingly, some of the isolates that displayed phenotypic resistance to these antimicrobials lacked the corresponding genetic determinants. Among erythromycin-resistant isolates, a diverse array of potential molecular resistance mechanisms was investigated, including the presence of ermB and mutations in the 23S rRNA gene, the rplD and rplV ribosomal genes, and the regulatory region of the cmeABC operon. Two of the four erythromycin-resistant isolates harboured the A2075G transition mutation in the 23S rRNA gene; one of these isolates exhibited further mutations in rplD, rplV and in the cmeABC regulatory region. This study expands the current understanding of how different genetic determinants and particular clones shape the epidemiology of antimicrobial resistance in C. jejuni in Belgium. It also reveals many questions in need of further investigation, such as the role of other undetermined molecular mechanisms that may potentially contribute to the antimicrobial resistance of Campylobacter.
Klebsiella pneumonia infection rates have increased dramatically. Molecular typing and virulence analysis are powerful tools that can shed light on Klebsiella pneumonia infections. Whereas 77.7% ...(28/36) of clinical isolates indicated multidrug resistant (MDR) patterns, 50% (18/36) indicated carpabenem resistance. Gene prevalence for the AcrAB efflux pump (82.14%) was more than that of the mdtK efflux pump (32.14%) in the MDR isolates. FimH-1 and mrkD genes were prevalent in wound and blood isolates. FimH-1 gene was prevalent in sputum while mrkD gene was prevalent in urine. Serum resistance associated with outer membrane protein coding gene (traT) was found in all blood isolates. IucC, entB, and Irp-1 were detected in 32.14%, 78.5% and 10.7% of MDR isolates, respectively. We used two Polymerase Chain Reaction (PCR) analyses: Enterobacterial Repetitive Intergenic Consensus (ERIC) and Random Amplified Polymorphic DNA (RAPD). ERIC-PCR revealed 21 and RAPD-PCR revealed 18 distinct patterns of isolates with similarity ≥80%. ERIC genotyping significantly correlated with resistance patterns and virulence determinants. RAPD genotyping significantly correlated with resistance patterns but not with virulence determinants. Both RAPD and ERIC genotyping methods had no correlation with the capsule types. These findings can help up better predict MDR Klebsiella pneumoniae outbreaks associated with specific genotyping patterns.
The purpose of this study was to: (i) evaluate the antibacterial activities of three Egyptian honeys collected from different floral sources (namely, citrus, clover, and marjoram) against Escherichia ...coli; (ii) investigate the effects of these honeys on bacterial ultrastructure; and (iii) assess the anti-virulence potential of these honeys, by examining their impacts on the expression of eight selected genes (involved in biofilm formation, quorum sensing, and stress survival) in the test organism. The minimum inhibitory concentration (MIC) of the honey samples against E. coli ATCC 8739 were assessed by the broth microdilution assay in the presence and absence of catalase enzyme. Impacts of the honeys on the cellular ultrastructure and the expression profiles of the selected genes of E. coli were examined using transmission electron microscopy (TEM) and quantitative real-time polymerase chain reaction (qPCR) analysis, respectively. The susceptibility tests showed promising antibacterial activities of all the tested honeys against E. coli. This was supported by the TEM observations, which revealed "ghost" cells lacking DNA, in addition to cells with increased vacuoles, and/or with irregular shrunken cytoplasm. Among the tested honeys, marjoram exhibited the highest total antibacterial activity and the highest levels of peroxide-dependent activity. The qPCR analysis showed that all honey-treated cells share a similar overall pattern of gene expression, with a trend toward reduced expression of the virulence genes of interest. Our results indicate that some varieties of the Egyptian honey have the potential to be effective inhibitor and virulence modulator of E. coli via multiple molecular targets.
Biofilm-formed enterococcal urinary tract clinical isolates (n = 92) were used for studying the antibiofilm activity of cinnamon, ginger, and chemical AgNPs. The average particle sizes of cinnamon, ...ginger, and chemical AgNPs were 8.7, 41.98, and 55.7 nm, respectively. The results of Fourier transform infrared analysis revealed that phytocompounds, such as cinnamaldehyde and gingerol, were the main compounds incorporated in the synthesis of cinnamon and ginger AgNPs, respectively. The purity and crystalline nature of the AgNPs have been confirmed by energy dispersive X-ray and X-ray Diffraction analysis. The results of antimicrobial activity showed that MIC of ginger, cinnamon, and chemical AgNPs were 37.64, 725.7, and 61.08 μg/ml, respectively. On studying the antibiofilm activity of AgNPs at sub-MIC values (1/2, 1/4, and 1/8 MIC), the results revealed that it was concentration dependent. Therefore, further studies were carried out to evaluate the antibiofilm activity of AgNPs at a concentration of 18 μg/ml. The results showed that ginger and chemical AgNPs reduced the formed biofilm to 39.14% and 65.32% and the number of adherent cells on the urinary catheter surface to 42.73% and 69.84%, respectively, as compared to that of the control, while cinnamon AgNPs showed no significant activity. Accordingly, ginger AgNPs had the most potent antibacterial and antiadherent activity against biofilm-associated enterococcal isolates.
Fluoroquinolones have been used for prophylaxis against infections in cancer patients but their impact on the resistance mechanisms still require further investigation. To elucidate mechanisms ...underlying ciprofloxacin (CIP) resistance in Gram-negative pathogens causing infections to cancer patients, 169 isolates were investigated. Broth microdilution assays showed high-level CIP resistance in 89.3% of the isolates. Target site mutations were analyzed using PCR and DNA sequencing in 15 selected isolates. Of them, all had gyrA mutations (codons 83 and 87) with parC mutations (codons 80 and 84) in 93.3%. All isolates were screened for plasmid-mediated quinolone resistance (PMQR) genes and 56.8% of them were positive in this respect. Among PMQR genes, aac(6')-Ib-cr predominated (42.6%) while qnr genes were harbored by 32.5%. This comprised qnrS in 26.6% and qnrB in 6.5%. Clonality of the qnr-positive isolates using ERIC-PCR revealed that most of them were not clonal. CIP MIC reduction by CCCP, an efflux pump inhibitor, was studied and the results revealed that contribution of efflux activity was observed in 18.3% of the isolates. Furthermore, most fluoroquinolone resistance mechanisms were detected among Gram-negative isolates recovered from cancer patients. Target site mutations had the highest impact on CIP resistance as compared to PMQRs and efflux activity.
Six compounds namely, tanshinone IIA (1), carnosic acid (2), rosmarinic acid (3), salvianolic acid B (4), baicalein (5), and glycyrrhetinic acid (6) were screened for their anti-SARS-CoV-2 activities ...against both the spike (S) and main protease (Mpro) receptors using molecular docking studies. Molecular docking recommended the superior affinities of both salvianolic acid B (4) and glycyrrhetinic acid (6) as the common results from the previously published computational articles. On the other hand, their actual anti-SARS-CoV-2 activities were tested
using plaque reduction assay to calculate their IC
values after measuring their CC
values using MTT assay on Vero E6 cells. Surprisingly, tanshinone IIA (1) was the most promising member with IC
equals 4.08 ng μl
. Also, both carnosic acid (2) and rosmarinic acid (3) showed promising IC
values of 15.37 and 25.47 ng μl
, respectively. However, salvianolic acid (4) showed a weak anti-SARS-CoV-2 activity with an IC
value equals 58.29 ng μl
. Furthermore, molecular dynamics simulations for 100 ns were performed for the most active compound from the computational point of view (salvianolic acid 4), besides, the most active one biologically (tanshinone IIA 1) on both the S and Mpro complexes of them (four different molecular dynamics processes) to confirm the docking results and give more insights regarding the stability of both compounds inside the SARS-CoV-2 mentioned receptors, respectively. Also, to understand the mechanism of action for the tested compounds towards SARS-CoV-2 inhibition it was necessary to examine the mode of action for the most two promising compounds, tanshinone IIA (1) and carnosic acid (2). Both compounds (1 and 2) showed very promising virucidal activity with a most prominent inhibitory effect on viral adsorption rather than its replication. This recommended the predicted activity of the two compounds against the S protein of SARS-CoV-2 rather than its Mpro protein. Our results could be very promising to rearrange the previously mentioned compounds based on their actual inhibitory activities towards SARS-CoV-2 and to search for the reasons behind the great differences between their
and
results against SARS-CoV-2. Finally, we recommend further advanced preclinical and clinical studies especially for tanshinone IIA (1) to be rapidly applied in COVID-19 management either alone or in combination with carnosic acid (2), rosmarinic acid (3), and/or salvianolic acid (4).
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