We synthesized a set of small molecules using a molecular hybridization approach with good yields. The antiviral properties of the synthesized conjugates against the SAR-CoV-2 virus were investigated ...and their cytotoxicity was also determined. Among all the synthesized conjugates, compound 9f showed potential against SARS-CoV-2 and low cytotoxicity. The conjugates’ selectivity indexes (SIs) were determined to correlate the antiviral properties and cytotoxicity. The observed biological data were further validated using computational studies.
Background
The burden of post-coronavirus disease (COVID)-19 symptoms has been increasing and is of great concern in patients with pre-existing chronic medical conditions.This study aimed to ...delineate the post-COVID-19 neuropsychiatric symptoms among migraine patients compared to the non-migraine control group.
Methods
Two groups, each of 204 COVID-19 survivors, were enrolled in the study after 3 months of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, one group fulfilling the episodic migraine criteria and the other serving as a matching control group. Subjects were evaluated through an in-person interview for post-COVID-19 neuropsychiatric symptoms, including detailed headache patterns and severity, using the visual analogue scale.
Results
The Frequency of headache during the acute phase of COVID-19 was more frequent in migraine patients (OR = 1.60, 95%CI = 1.04–2.45,
P-
value = 0.031). The reported significant post-COVID-19 neuropsychiatric symptoms in migraine patients compared to controls were fatigue (OR = 1.662, 95%CI = 1.064–2.596,
P-
value = 0.025), anosmia/hyposmia (OR = 2.06, 95%CI = 1.164- 3.645,
P-
value = 0.012), cacosmia (OR = 2.663, 95%CI = 1.145–6.195,
P-
value = 0.019), depression (OR = 2.259, 95%CI = 1.284- 3.975,
P-
value = 0.004), anxiety (OR = 3.267, 95%CI = 1.747- 6.108,
P-
value ≤ 0.001), insomnia (OR = 2.203, 95%CI = 1.298- 3.739,
P-
value = 0.003), and headache (OR = 3.148, 95%CI = 1.616–6.136,
P-
value = ≤ 0.001).While there was no statistically significant difference between migraine patients and controls regarding the post-COVID-19 functional status score (
P-
value = 0.102). The pattern of post-COVID-19 headache was reported as chronic headache transformation in 17.6% of the migraine group, with the median intensity rate being 5.5 and IQR (3–7). In the control group, 14% experienced chronic headache attributed to systemic viral infection with a median intensity rate of 2 and IQR (2–5), while 12% experienced a new daily persistent headache with a median intensity of 5 and IQR (1–6).
Conclusion
The study highlighted the importance of follow-up migraine patients upon recovery from COVID-19 infection, being more vulnerable to post-COVID-19 symptoms.
The potential long-term neuropsychiatric effects of COVID-19 are of global concern. This study aimed to determine the prevalence and predictors of neuropsychiatric post-acute sequelae of COVID-19 ...among Egyptian COVID-19 survivors and to study the impact of full vaccination before COVID-19 infection on the occurrence and severity of these manifestations. Three months after getting COVID-19 infection, 1638 COVID-19 survivors were screened by phone for possible neuropsychiatric sequelae. Subjects suspected to suffer from these sequelae were invited to a face-to-face interview for objective evaluation. They were requested to rate the severity of their symptoms using visual analogue scales (VAS). The mean age of participants was 38.28 ± 13 years. Only 18.6% were fully vaccinated before COVID-19 infection. Neuropsychiatric post-acute sequelae of COVID-19 were documented in 598 (36.5%) subjects, fatigue was the most frequent one (24.6%), followed by insomnia (16.4%), depression (15.3%), and anxiety (14.4%). Moderate and severe COVID-19 infection and non-vaccination increased the odds of developing post-COVID-19 neuropsychiatric manifestations by 2 times (OR 1.95, 95% CI = 1.415–2.683), 3.86 times (OR 3.86, 95% CI = 2.358–6.329), and 1.67 times (OR 1.67, 95% CI = 1.253–2.216), respectively. Fully vaccinated subjects before COVID-19 infection (
n
= 304) had significantly lesser severity of post-COVID-19 fatigue, ageusia/hypogeusia, dizziness, tinnitus, and insomnia (
P
value = 0.001, 0.008, < 0.001, 0.025, and 0.005, respectively) than non-vaccinated subjects. This report declared neuropsychiatric sequelae in 36.5% of Egyptian COVID-19 survivors, fatigue being the most prevalent. The effectiveness of COVID-19 vaccines in reducing the severity of some post-COVID-19 neuropsychiatric manifestations may improve general vaccine acceptance.
Background
SARS-CoV-2 infection involves disturbing multiple molecular pathways related to immunity and cellular functions. PIM1 is a serine/threonine-protein kinase found to be involved in the ...pathogenesis of several viral infections. One PIM1 substrate, Myc, was reported to interact with TMPRSS2, which is crucial for SARS-CoV-2 cell entry. PIM1 inhibitors were reported to have antiviral activity through multiple mechanisms related to immunity and proliferation. This study aimed to evaluate the antiviral activity of
2-pyridone PIM1 inhibitor
against SARS-CoV-2 and its potential role in hindering the progression of COVID-19. It also aimed to assess PIM1 inhibitor’s effect on the expression of several genes of Notch signaling and Wnt pathways. In vitro study was conducted on Vero-E6 cells infected by SARS-CoV-2 “NRC-03-nhCoV” virus. Protein–protein interaction of the study genes was assessed to evaluate their relation to cell proliferation and immunity. The effect of
2-pyridone PIM1 inhibitor
treatment on viral load and mRNA expression of target genes was assessed at three time points.
Results
Treatment with
2-pyridone PIM1 inhibitor
showed potential antiviral activity against SARS-CoV-2 (IC
50
of 37.255 µg/ml), significantly lowering the viral load. Functional enrichments of the studied genes include negative regulation of growth rate, several biological processes involved in cell proliferation, and Interleukin-4 production, with interleukin-6 as a predicted functional partner. These results suggest an interplay between study genes with relation to cell proliferation and immunity. Following in vitro SARS-CoV-2 infection, Notch pathway genes, CTNNB1, SUMO1, and TDG, were found to be overexpressed compared to uninfected cells. Treatment with
2-pyridone PIM1 inhibitor
significantly lowers the expression levels of study genes, restoring Notch1 and BCL9 to the control level while decreasing Notch2 and CTNNB1 below control levels.
Conclusion
2-pyridone PIM1 inhibitor
could hinder cellular entry of SARS-CoV-2 and modulate several pathways implicated in immunity, suggesting a potential benefit in the development of anti-SARS-CoV-2 therapeutic approach.
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a patient with acute pneumonia and renal failure in Saudi Arabia in 2012. By July 2023, MERS-CoV had resulted in ...2605 human cases worldwide, causing a fatality rate of 36%, with 90.2% of cases being located in the Arabian Peninsula. The dromedary camel (Camelus dromedarius) is presumed to be an intermediate host for viral transmission to humans. So far, no prophylactic vaccines or effective antiviral treatments have been approved for MERS-CoV. RNA silencing is a novel approach for treating several diseases. A web-based bioinformatics tool (i-Score Designer) with integrative computational methods was used to predict and evaluate the designed siRNAs. This approach enabled the targeting of a highly conserved region of the MERS-CoV membrane (M) gene to inhibit virus replication. siRNA-M1, -M2, and -M3 were selected as the best of 559 designed siRNA candidates for an in vitro validation based on 2nd generation algorithm scoring, thermodynamic properties, off-target filtration, position-specific nucleotide preferences, and a free immune-stimulatory motifs. siRNAs were evaluated in Vero cells for their cytotoxicity and antiviral efficacy in vitro. Our results showed that the predicted siRNAs had no apparent cytotoxicity observed in Vero cells. The obtained results from the plaque reduction assay and RT-qPCR indicated that siRNA-M3 was the best candidate to inhibit MERS-CoV replication with a defined concentration of 400 picoMolar (pM). The computational methods used, and the in vitro evaluation, may provide an insight for a new antiviral strategy against MERS-CoV, a further in vivo study will nevertheless be required.
Using convalescent plasma as immunotherapy is an old method for treatment of infectious diseases. Several countries have recently allowed the use of such therapy for the treatment of COVID-19 ...patients especially those who are critically ill. A similar program is currently being tested in Egypt. Here, we tested 227 plasma samples from convalescent donors in Egypt for neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a microneutralization (MN) assay. A third of the tested samples did not have antibody titers and 58% had titers between 1:10 and 1:80. Only 12% had titers >1:160. We also compared MN assays using different virus concentrations, plaque reduction neutralization (PRNT) assays, and a chemiluminescence assay that measures immunoglobulin G (IgG) binding to N and S proteins of SARS-CoV-2. Our results indicated that a MN assay using 100 TCID50/ml provides comparable results to PRNT and allows for high throughput testing.
Vaccination is the most functional medical intervention to prophylactically control severe diseases caused by human-to-human or animal-to-human transmissible viral pathogens. Annually, seasonal ...influenza epidemics attack human populations leading to 290-650 thousand deaths/year worldwide. Recently, a novel Middle East Respiratory Syndrome Coronavirus emerged. Together, those two viruses present a significant public health burden in areas where they circulate. Herein, we generated a bacterial outer membrane vesicles (OMVs)-based vaccine presenting the antigenic stable chimeric fusion protein of the H1-type haemagglutinin (HA) of the pandemic influenza A virus (H1N1) strain from 2009 (H1N1pdm09) and the receptor binding domain (RBD) of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (OMVs-H1/RBD). Our results showed that the chimeric antigen could induce specific neutralizing antibodies against both strains leading to protection of immunized mice against H1N1pdm09 and efficient neutralization of MERS-CoV. This study demonstrate that OMVs-based vaccines presenting viral antigens provide a safe and reliable approach to protect against two different viral infections.
Type 2 diabetes mellitus (T2DM) is a major global health concern. It usually develops gradually and is frequently preceded by undetectable pre-diabetes mellitus (pre-DM) stage. The purpose of this ...study was to identify a novel set of seven candidate genes associated with the pathogenesis of insulin resistance (IR) and pre-DM, followed by their experimental validation in patients' serum samples.
We used the bioinformatics tools and through a two-step process, we first identified and verified two mRNA candidate genes linked to insulin resistance molecular pathogenesis. Second, we identified a non-coding RNAs related to the selected mRNAs and implicated in the insulin resistance molecular pathways followed by pilot study for the RNA panel differential expression in 66 patients with T2DM, 49 individuals with prediabetes and 45 matched controls using real time PCR.
The levels of expression of TMEM173 and CHUK mRNAs, hsa-miR (-611, -5192, and -1976) miRNAs gradually increased from the healthy control group to the prediabetic group, reaching their maximum levels in the T2DM group (p <10-3), whereas the levels of expression of RP4-605O3.4 and AC074117.2 lncRNAs declined gradually from the healthy control group to the prediabetic group, reaching their lowest levels in the T2DM group (p <10-3). TMEM173, CHUK mRNAs, hsa_miR (-611 & -1976) and RP4-605O3.4 lncRNA were useful in distinguishing insulin resistant from insulin sensitive groups. miR_611 together with RP4-605O3.4 exhibited significant difference in good versus poor glycemic control groups.
The presented study provides an insight about this RNA based STING/NOD/IR associated panel that could be used for PreDM-T2DM diagnosis and also as a therapeutic target based on the differences of its expression level in the pre-DM and T2DM stages.
Controlling avian influenza viruses (AIVs) is mainly based on culling of the infected bird flocks or via the implementation of inactivated vaccines in countries where AIVs are considered to be ...endemic. Over the last decade, several avian influenza virus subtypes, including highly pathogenic avian influenza (HPAI) H5N1 clade 2.2.1.2, H5N8 clade 2.3.4.4b and the recent H5N1 clade 2.3.4.4b, have been reported among poultry populations in Egypt. This demanded the utilization of a nationwide routine vaccination program in the poultry sector. Antigenic differences between available avian influenza vaccines and the currently circulating H5Nx strains were reported, calling for an updated vaccine for homogenous strains. In this study, three H5Nx vaccines were generated by utilizing the reverse genetic system: rgH5N1_2.3.4.4, rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2. Further, the immunogenicity and the cross-reactivity of the generated inactivated vaccines were assessed in the chicken model against a panel of homologous and heterologous H5Nx HPAIVs. Interestingly, the rgH5N1_2.3.4.4 induced high immunogenicity in specific-pathogen-free (SPF) chicken and could efficiently protect immunized chickens against challenge infection with HPAIV H5N1_2.3.4.4, H5N8_2.3.4.4 and H5N1_2.2.1.2. In parallel, the rgH5N1_2.2.1.2 could partially protect SPF chickens against infection with HPAIV H5N1_2.3.4.4 and H5N8_2.3.4.4. Conversely, the raised antibodies to rgH5N1_2.3.4.4 could provide full protection against HPAIV H5N1_2.3.4.4 and HPAIV H5N8_2.3.4.4, and partial protection (60%) against HPAIV H5N1_2.2.1.2. Compared to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2 vaccines, chickens vaccinated with rgH5N1_2.3.4.4 showed lower viral shedding following challenge infection with the predefined HPAIVs. These data emphasize the superior immunogenicity and cross-protective efficacy of the rgH5N1_2.3.4.4 in comparison to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2.
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not ...well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.
Emerging Microbes & Infections (2017) 6, e1; doi:
10.1038/emi.2016.130
; published online 4 January 2017
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