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1.
Arch Virol ; 169(5): 95, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594485

RESUMEN

The first detection of a human infection with avian influenza A/H6N1 virus in Taiwan in 2013 has raised concerns about this virus. During our routine surveillance of avian influenza viruses (AIVs) in live-bird markets in Egypt, an H6N1 virus was isolated from a garganey duck and was characterized. Phylogenetic analysis indicated that the Egyptian H6N1 strain A/Garganey/Egypt/20869C/2022(H6N1) has a unique genomic constellation, with gene segments inherited from different subtypes (H5N1, H3N8, H7N3, H6N1, and H10N1) that have been detected previously in AIVs from Egypt and some Eurasian countries. We examined the replication of kinetics of this virus in different mammalian cell lines (A549, MDCK, and Vero cells) and compared its pathogenicity to that of the ancestral H6N1 virus A/Quail/HK/421/2002(H6N1). The Egyptian H6N1 virus replicated efficiently in C57BL/6 mice without prior adaptation and grew faster and reached higher titers than in A549 cells than the ancestral strain. These results show that reassortant H6 AIVs might pose a potential threat to human health and highlight the need to continue surveillance of H6 AIVs circulating in nature.


Asunto(s)
Subtipo H3N8 del Virus de la Influenza A , Subtipo H5N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Animales , Ratones , Chlorocebus aethiops , Humanos , Gripe Aviar/epidemiología , Egipto/epidemiología , Filogenia , Células Vero , Subtipo H7N3 del Virus de la Influenza A , Ratones Endogámicos C57BL , Animales Salvajes , Patos , Mamíferos
2.
Nat Commun ; 15(1): 3450, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664395

RESUMEN

Influenza A viruses (IAVs) of subtype H9N2 have reached an endemic stage in poultry farms in the Middle East and Asia. As a result, human infections with avian H9N2 viruses have been increasingly reported. In 2017, an H9N2 virus was isolated for the first time from Egyptian fruit bats (Rousettus aegyptiacus). Phylogenetic analyses revealed that bat H9N2 is descended from a common ancestor dating back centuries ago. However, the H9 and N2 sequences appear to be genetically similar to current avian IAVs, suggesting recent reassortment events. These observations raise the question of the zoonotic potential of the mammal-adapted bat H9N2. Here, we investigate the infection and transmission potential of bat H9N2 in vitro and in vivo, the ability to overcome the antiviral activity of the human MxA protein, and the presence of N2-specific cross-reactive antibodies in human sera. We show that bat H9N2 has high replication and transmission potential in ferrets, efficiently infects human lung explant cultures, and is able to evade antiviral inhibition by MxA in transgenic B6 mice. Together with its low antigenic similarity to the N2 of seasonal human strains, bat H9N2 fulfils key criteria for pre-pandemic IAVs.


Asunto(s)
Quirópteros , Hurones , Subtipo H9N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Replicación Viral , Animales , Hurones/virología , Subtipo H9N2 del Virus de la Influenza A/genética , Subtipo H9N2 del Virus de la Influenza A/fisiología , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Quirópteros/virología , Humanos , Infecciones por Orthomyxoviridae/transmisión , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/inmunología , Ratones , Filogenia , Gripe Humana/transmisión , Gripe Humana/virología , Pulmón/virología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre
3.
Nat Commun ; 15(1): 3449, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664384

RESUMEN

In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2). The virus has a pH inactivation profile and neuraminidase activity similar to those of human-adapted IAVs. Despite the virus having an avian virus-like preference for α2,3 sialic acid receptors, it is unable to replicate in male mallard ducks; however, it readily infects ex-vivo human respiratory cell cultures and replicates in the lungs of female mice. A/bat/Egypt/381OP/2017 replicates in the upper respiratory tract of experimentally-infected male ferrets featuring direct-contact and airborne transmission. These data suggest that the bat A(H9N2) virus has features associated with increased risk to humans without a shift to a preference for α2,6 sialic acid receptors.


Asunto(s)
Quirópteros , Patos , Hurones , Subtipo H9N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Receptores de Superficie Celular , Animales , Quirópteros/virología , Humanos , Hurones/virología , Femenino , Masculino , Subtipo H9N2 del Virus de la Influenza A/fisiología , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/transmisión , Ratones , Patos/virología , Replicación Viral , Gripe Humana/virología , Gripe Humana/transmisión , Pulmón/virología , Gripe Aviar/virología , Gripe Aviar/transmisión , Neuraminidasa/metabolismo
4.
Influenza Other Respir Viruses ; 18(2): e13257, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38342948

RESUMEN

We share the experience of research laboratories in the Eastern Mediterranean Region (EMR) that contributed to preparedness and response to highly pathogenic avian influenza (HPAI), Middle-East respiratory syndrome coronavirus (MERS-CoV), and coronavirus disease (COVID-19). Research groups in the region were pivotal in identifying, characterizing the pathogens and describing their evolution, distribution, transmission routes, and the immunological profile of exposed populations. They demonstrated the capacity to develop and test antivirals and potential vaccines. The EMR experience is a model of how national systems can work with researchers to improve regional preparedness and response to future epidemics and pandemics.


Asunto(s)
COVID-19 , Gripe Aviar , Coronavirus del Síndrome Respiratorio de Oriente Medio , Humanos , Animales , Pandemias/prevención & control , Gripe Aviar/epidemiología , COVID-19/epidemiología , Laboratorios , Región Mediterránea/epidemiología
5.
Arch Public Health ; 82(1): 6, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216978

RESUMEN

PURPOSE: To describe the changes that occurred in the SARS-CoV-2 and influenza Prevalence, epidemiology, clinical picture, and prevalent genotypes among the Egyptian pilgrims returning from Hajj and Umrah 2022 seasons. METHODS: Pilgrims were contacted at the airport and invited to participate in the survey. Pilgrims who consented were interviewed using a standardized line list that included participant demographics, respiratory symptoms if any, previous COVID-19 infection, influenza vaccination whereas COVID-19 vaccination information were collected from vaccination cards. Participants were asked to provide throat and nasopharyngeal swabs for SARS-CoV-2 and influenza testing using RT-PCR and a subset of isolates were sequenced. Descriptive data analysis was performed to describe the epidemiology and clinical symptoms of SARS-CoV-2 and influenza. Prevalence rates of SARS-CoV-2 and influenza during Hajj were calculated and compared to Umrah surveys using chi2 and t-test with a significance level < 0.05. RESULTS: Overall, 3,862 Egyptian pilgrims enrolled, their mean age was 50.5 ± 47 years, half of them were > 50 years of age and 58.2% were males. Of them, 384 (9.9%) tested positive for SARS-CoV-2 and 51 (1.3%) for influenza viruses. Prevalence of SARS-CoV-2 infections (vaccine breakthrough) increased significantly between the Umrah and Hajj surveys (6.7% vs. 9.9%, p < 0.001), and variants of the virus varied considerably. Whereas no significant difference was found in influenza prevalence, vaccine coverage and vaccine breakthrough infection rates (11.7 vs. 9.2%, 26.9 vs. 26.8%, and 1.4 vs. 1.1% respectively). CONCLUSIONS: SARS-CoV-2 prevalence among Egyptian pilgrims returning from Hajj in July increased with reduced vaccine effectiveness compared to Umrah in March 2022 suggesting a possible wave of SARS-CoV-2 in the upcoming winter.

6.
Sci Rep ; 13(1): 21860, 2023 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-38071208

RESUMEN

In late 2022, severe acute respiratory infections (SARI) surveillance reported an abrupt increase in non-COVID-19 infections among children after three years of drastic reductions. Signals of increased absenteeism due to respiratory symptoms among primary and preparatory school children were detected by Event-Based Surveillance. We conducted a hospital-based survey of children who were admitted with SARI to identify the causative pathogen(s) and estimate the burden of infection. A survey was conducted among children < 16 years in 21 referral hospitals in the three governorates with the highest SARI rates. Patients' demographics, clinical symptoms, and severity were collected from medical records using a line list. Patients were swabbed and tested for a panel of 33 respiratory pathogens by RT-PCR at the Central Laboratory in Cairo. Descriptive data analysis was performed for demographic data. Patients' characteristics were compared by causative agents' clinical picture and severity using Chi2 with a p < 0.05 significance. Overall, 317 patients were enrolled, 58.3% were ≤ 1 year of age, 61.5% were males. Of 229 (72.7%) of positively tested patients, viruses caused 92.1% including RSV 63.8%, Rhinovirus 10.0%, Influenza 9.2%, Adenovirus 5.2%, and 1.3% co-infected with two viruses. Bacteria caused 3.5% of cases and 4.4% had mixed viral-bacterial infections. Rhinovirus was the most common cause of death among children with SARI, followed by RSV (8.7% and 1.4%), whereas influenza and Adenovirus did not result in any deaths. Patients with viral-bacterial infections are more likely to be admitted to ICU and die at the hospital than bacterial or viral infections (60% and 20% vs. 31.8% and 1.9% vs. 12.5% and 12.5%, p < 0.001). Viruses particularly RSV are the leading cause of SARI causing significant health problem among children < 16 years in Egypt. Bacterial on top of viral infection can worsen disease courses and outcomes. Studies are required to estimate the SARI burden accurately among Egyptian children and a comprehensive approach tailored to Egypt is necessary to reduce its burden.


Asunto(s)
Infecciones por Adenoviridae , Infecciones Bacterianas , Gripe Humana , Neumonía , Infecciones del Sistema Respiratorio , Virosis , Niño , Femenino , Humanos , Lactante , Masculino , Niño Hospitalizado , Egipto/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Rhinovirus , Preescolar , Adolescente
7.
Microorganisms ; 11(11)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38004788

RESUMEN

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.

8.
Nature ; 622(7984): 810-817, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37853121

RESUMEN

Highly pathogenic avian influenza (HPAI) H5N1 activity has intensified globally since 2021, increasingly causing mass mortality in wild birds and poultry and incidental infections in mammals1-3. However, the ecological and virological properties that underscore future mitigation strategies still remain unclear. Using epidemiological, spatial and genomic approaches, we demonstrate changes in the origins of resurgent HPAI H5 and reveal significant shifts in virus ecology and evolution. Outbreak data show key resurgent events in 2016-2017 and 2020-2021, contributing to the emergence and panzootic spread of H5N1 in 2021-2022. Genomic analysis reveals that the 2016-2017 epizootics originated in Asia, where HPAI H5 reservoirs are endemic. In 2020-2021, 2.3.4.4b H5N8 viruses emerged in African poultry, featuring mutations altering HA structure and receptor binding. In 2021-2022, a new H5N1 virus evolved through reassortment in wild birds in Europe, undergoing further reassortment with low-pathogenic avian influenza in wild and domestic birds during global dissemination. These results highlight a shift in the HPAI H5 epicentre beyond Asia and indicate that increasing persistence of HPAI H5 in wild birds is facilitating geographic and host range expansion, accelerating dispersion velocity and increasing reassortment potential. As earlier outbreaks of H5N1 and H5N8 were caused by more stable genomic constellations, these recent changes reflect adaptation across the domestic-bird-wild-bird interface. Elimination strategies in domestic birds therefore remain a high priority to limit future epizootics.


Asunto(s)
Aves , Brotes de Enfermedades , Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar , Internacionalidad , Animales , África/epidemiología , Animales Salvajes/virología , Asia/epidemiología , Aves/virología , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Brotes de Enfermedades/veterinaria , Europa (Continente)/epidemiología , Evolución Molecular , Especificidad del Huésped , Subtipo H5N1 del Virus de la Influenza A/clasificación , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Subtipo H5N8 del Virus de la Influenza A/genética , Subtipo H5N8 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/epidemiología , Gripe Aviar/mortalidad , Gripe Aviar/transmisión , Gripe Aviar/virología , Mamíferos/virología , Mutación , Filogenia , Aves de Corral/virología
9.
Int J Pharm ; 646: 123385, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37678473

RESUMEN

The evolution of a safe and effective therapeutic system to conquer SAR-CoV-2 infection deemed to be a crucial worldwide demand. Curcumin (CUR) is a phytomedicinal polyphenolic drug that exhibited a well-reported anti-SAR-CoV-2. However, the therapeutic activity of CUR is hindered by its poor intestinal permeability and diminished aqueous solubility. Therefore, this study strived to develop D-alpha-tocopheryl polyethylene glycol succinate (TPGS) bilosomes (TPGS-Bs) adopting 23 full factorial designs to improve solubility and intestinal permeability of CUR, hence boosting its anti-SARS-CoV-2 activity. Eight experimental runs were attained considering three independent variables: soybean phosphatidylcholine amount (mg) (SPC amount), bile salt amount (mg) (BS amount), and TPGS amount (mg). The optimum formula (F4) exhibited EE % (88.5 ± 2.4 %), PS (181.5 ± 21.6 nm), and ZP (-34.5 ± 3.7 mV) with desirability value = 0.739 was picked as an optimum formula. Furthermore, the optimum formula (F4) was extra coated with chitosan (CS) to improve permeability and anti-SAR-CoV-2 activity. Caco-2 cell uptake after 2 hr revealed the superiority of CS-F4 and F4 by 6 and 5 folds relative to CUR dispersion, respectively. Furthermore, CS-F4 exhibited a significantly higher anti-SARS-CoV-2 activity with IC50 (0.24 µg/ml) by 8.3 times than F4 (1.99 µg/ml). Besides, the mechanistic study demonstrated that the two formulae imparted antiviral activity by inhibiting the spike protein by virucidal potentialities. In addition, the conducted molecular docking and MD simulations towards the SARS-CoV-2 Mpro enzyme confirmed the interaction of CUR with key residues of the virus enzymes. Based on the preceded, CS-F4 could be assumed to be used to effectively eradicate SARS-CoV-2 infection.

10.
BMC Infect Dis ; 23(1): 542, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37596534

RESUMEN

BACKGROUND: The o severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic has killed millions of people and caused widespread concern around the world. Multiple genetic variants of SARS-CoV-2 have been identified as the pandemic continues. Concerns have been raised about high transmissibility and lower vaccine efficacy against omicron. There is an urgent need to better describe how omicron will impact clinical presentation and vaccine efficacy. This study aims at comparing the epidemiologic, clinical, and genomic characteristics of the omicron variant prevalent during the fifth wave with those of other VOCs between May 2020 and April 2022. METHODS: Epidemiological data were obtained from the National Electronic Diseases Surveillance System. Secondary data analysis was performed on all confirmed COVID-19 patients. Descriptive data analysis was performed for demographics and patient outcome and the incidence of COVID-19 was calculated as the proportion of SARS-CoV-2 confirmed patients out of the total population of Egypt. Incidence and characteristics of the omicron cohort from January- April 2022, were compared to those confirmed from May 2020-December 2021. We performed the whole-genome sequencing of SARS-CoV-2 on 1590 specimens using Illumina sequencing to describe the circulation of the virus lineages in Egypt. RESULTS: A total of 502,629 patients enrolled, including 60,665 (12.1%) reported in the fifth wave. The incidence rate of omicron was significantly lower than the mean of incidences in the previous subperiod (60.1 vs. 86.3/100,000 population, p < 0.001). Symptoms were reported less often in the omicron cohort than in patients with other variants, with omicron having a lower hospitalization rate and overall case fatality rate as well. The omicron cohort tended to stay fewer days at the hospital than did those with other variants. We analyzed sequences of 2433 (1590 in this study and 843 were obtained from GISAID platform) Egyptian SARS-CoV-2 full genomes. The first wave that occurred before the emergence of global variants of concern belonged to the B.1 clade. The second and third waves were associated with C.36. Waves 4 and 5 included B.1.617.2 and BA.1 clades, respectively. CONCLUSIONS: The study indicated that Omicron-infected patients had milder symptoms and were less likely to be hospitalized; however, patients hospitalized with omicron had a more severe course and higher fatality rates than those hospitalized with other variants. Our findings demonstrate the importance of combining epidemiological data and genomic analysis to generate actionable information for public health decision-making.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Egipto/epidemiología , Gravedad del Paciente , Evolución Molecular
11.
Virol J ; 20(1): 170, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37533069

RESUMEN

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.


Asunto(s)
Infecciones del Sistema Nervioso Central , Enterovirus , Infecciones por Virus de Epstein-Barr , Virosis , Virus , Humanos , Masculino , Egipto/epidemiología , Herpesvirus Humano 4/genética , Reacción en Cadena de la Polimerasa/métodos , Virosis/epidemiología , Infecciones del Sistema Nervioso Central/epidemiología , Herpesvirus Humano 3/genética , Herpesvirus Humano 2 , ADN Viral
13.
Pathogens ; 12(7)2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37513723

RESUMEN

Bats are considered the main reservoir of coronaviruses (CoVs), and research evidence suggests the essential role of bats in the emergence of Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoV) and SARS-CoV-2. SARS-CoV-like viruses have been recently detected in bats in different countries. In 2020, we conducted surveillance for CoVs among six different bat species in Lebanon. Of 622 swab specimens taken, 77 tested positive. Alpha- and Beta- CoVs were identified in samples collected from different species. Our results show that SARS-like coronaviruses circulate in bats in this region, and we provide new data on their genetic diversity. The interaction between the spike of the detected SARS-CoV-like viruses and the human angiotensin-converting enzyme 2 (hACE2) receptor could be crucial in understanding the origin of the epidemic. The 3D protein structure analysis revealed that the receptor-binding domains of the SARS-like virus identified in Lebanon bind to the hACE2 protein more efficiently than to the spike of the SARS-CoV-2 strain. The spike of the detected SARS-CoV-like viruses does not contain the recognition site of furin at the cleavage site. Thus, our study highlights the variety of bat coronaviruses in Lebanon and suggests the zoonotic potential for other SARS-CoV-like viruses.

14.
Microbiol Resour Announc ; 12(6): e0000623, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37154755

RESUMEN

Monkeypox virus has recently been detected in multiple countries. Two cases of monkeypox virus were reported in Egypt as part of an ongoing international outbreak. We report the whole-genome sequence of a monkeypox virus that was retrieved from the first confirmed case in Egypt. The virus was fully sequenced on the Illumina platform, and phylogenetic analysis demonstrated that the current monkeypox strain is closely related to clade IIb, which caused recent multicountry outbreaks.

15.
J Enzyme Inhib Med Chem ; 38(1): 2202357, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37092260

RESUMEN

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a-g) were assessed in Vero E6 cells via MTT assay to calculate the CC50 and inhibitory concentration 50 (IC50) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with an IC50 value of 0.73 µg/mL. Moreover, F3e was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition. Besides, molecular docking and MD simulations towards the SARS-CoV-2 Mpro were performed. Finally, a structure-activity relationship (SAR) study focussed on studying the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide in addition to compound contraction on SARS-CoV-2 activity.HighlightsEmulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g).The most potent 3e-loaded EMLs (F3e) showed an IC50 value of 0.73 µg/mL against SARS-CoV-2.F3e exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition.Molecular docking, molecular dynamics (MD) simulations, and MM-GBSA calculations were performed.Structure-activity relationship (SAR) study was discussed to study the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide on the anti-SARS-CoV-2 activity.


Asunto(s)
COVID-19 , Nanopartículas , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Antivirales/farmacología , Simulación de Dinámica Molecular , Inhibidores de Proteasas
16.
Arch Virol ; 168(3): 82, 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36757481

RESUMEN

Active surveillance and studying the virological features of avian-origin influenza viruses are essential for early warning and preparedness for the next potential pandemic. During our active surveillance of avian influenza viruses in wild birds in Egypt in the period 2014-2017, multiple reassortant low-pathogenic avian influenza H7N3 viruses were isolated. In this study, we investigated and compared the infectivity, pathogenicity, and transmission of four different constellation forms of Egyptian H7N3 viruses in chickens and mice and assessed the sensitivity of these viruses to different commercial antiviral drugs in vitro. Considerable variation in virus pathogenicity was observed in mice infected with different H7N3 viruses. The mortality rate ranged from 20 to 100% in infected mice. Infected chickens showed only ocular clinical signs at three days postinfection as well as systemic viral infection in different organs. Efficient virus replication and transmission in chickens was observed within each group, indicating that these subtypes can spread easily from wild birds to poultry without prior adaptation. Mutations in the viral proteins associated with antiviral drug resistance were not detected, and all strains were sensitive to the antiviral drugs tested. In conclusion, all of the viruses studied had the ability to infect mice and chickens. H7N3 viruses circulating among wild birds in Egypt could threaten poultry production and public health.


Asunto(s)
Subtipo H7N3 del Virus de la Influenza A , Gripe Aviar , Animales , Ratones , Subtipo H7N3 del Virus de la Influenza A/genética , Pollos , Egipto/epidemiología , Antivirales/farmacología , Animales Salvajes , Aves de Corral , Virus Reordenados/genética , Filogenia
17.
Microb Pathog ; 174: 105928, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36470346

RESUMEN

Multiple incursions of different subtypes of highly pathogenic avian influenza (HPAI) A/H5NX viruses have caused widely considerable outbreaks in poultry and hundreds of human infections. Extensive reassortment events associated with currently circulating clade 2.3.4.4b of A/H5NX viruses have been widely recorded. Wild migratory birds contribute to the spillover of diverse viruses throughout their migration flyways. During our active surveillance of avian influenza in Egypt, we successfully isolated and fully characterized HPAI A/H5N5 virus of clade 2.3.4.4b that was detected in a healthy purple heron. The Egyptian H5N5 virus is genotypically similar with the same subtype that was detected in the far east of Russia and several European countries. The antigenic analysis showed that the Egyptian H5N5 virus is distinct from HPAI A(H5N8) viruses in Egypt. The virus preferentially binds to avian-like receptors rather than human-like receptors. Our results showed that the virus caused 100% and 60% lethality in chicken and mice respectively. Increasing active surveillance efforts, monitoring the dynamics of emerging AIVs, and risk assessment implementation should be globally applied especially in hot spot regions like Egypt.


Asunto(s)
Subtipo H5N8 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Humanos , Animales , Ratones , Gripe Aviar/epidemiología , Egipto/epidemiología , Filogenia , Animales Salvajes , Subtipo H5N8 del Virus de la Influenza A/genética , Pollos
18.
J Infect Public Health ; 15(11): 1290-1296, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36274370

RESUMEN

BACKGROUND: Ramadan Umrah is the second largest Islamic pilgrimage with 2.75 million pilgrims allowed in 2022. This report presents the results of a survey among Egyptian pilgrims returning from Ramadan Umrah to monitor SARS-CoV-2 and influenza activity and identify prevalent SARS-CoV-2 variants after this mass gathering. METHODS: Cross-sectional survey conducted at Cairo airport from 30th April 2022-5 th May 2022. Pilgrims were invited to participate voluntarily. After consenting, participants interviewed using questionnaire including demographics, health status, and vaccination information and asked to provide NP/OP swabs for SARS-CoV-2 and influenza testing by RT-PCR. Whole-genome sequencing performed for 29 SARS-CoV-2 isolates. Incidence calculated, descriptive data analysis performed, and SARS-CoV-2 patients were compared to negatively tested participants using chi2 and p value< 0.05. RESULTS: Overall, 1003 subjects participated, their mean age 50.9 ± 13 years, 594 (59.2%) were males. Of them, 76(7.6%) tested positive including 67(6.7%) SARS-CoV-2, 7(0.7%) influenza and 2(0.2%) SARS-CoV-2/influenza coinfection. Omicron sublineage BA.2 was the prevalent variant with no difference in severity identified between BA.1 and BA.2. No difference was identified between COVID-19 incidence among receivers of different vaccine types or between fully vaccinated and booster dose receivers. CONCLUSIONS: Survey indicated a low incidence of SARs-CoV-2 and influenza among Egyptian pilgrims returning from Ramadan Umrah. Patients had mild or no symptoms with no hospitalization or deaths reported. Full vaccination and booster doses of COVID-19 vaccines proved equally effective. Enhancing COVID-19 and influenza vaccination before mass gatherings and close monitoring of respiratory viruses among pilgrims returning from Hajj and Umrah are crucial for outbreak early detection and mitigation.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Orthomyxoviridae , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Arabia Saudita/epidemiología , Reuniones Masivas , Egipto/epidemiología , SARS-CoV-2/genética , Incidencia , Estudios Transversales , Vacunas contra la COVID-19 , COVID-19/epidemiología , Factores de Riesgo , Viaje
19.
Viruses ; 14(9)2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-36146685

RESUMEN

COVID-19 was first diagnosed in Egypt on 14 February 2020. By the end of November 2021, over 333,840 cases and 18,832 deaths had been reported. As part of the national genomic surveillance, 1027 SARS-CoV-2 near whole-genomes were generated and published by the end of July 2021. Here we describe the genomic epidemiology of SARS-CoV-2 in Egypt over this period using a subset of 976 high-quality Egyptian genomes analyzed together with a representative set of global sequences within a phylogenetic framework. A single lineage, C.36, introduced early in the pandemic was responsible for most of the cases in Egypt. Furthermore, to remain dominant in the face of mounting immunity from previous infections and vaccinations, this lineage acquired several mutations known to confer an adaptive advantage. These results highlight the value of continuous genomic surveillance in regions where VOCs are not predominant and the need for enforcement of public health measures to prevent expansion of the existing lineages.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Egipto/epidemiología , Humanos , Mutación , Pandemias , Filogenia , SARS-CoV-2/genética
20.
Viruses ; 14(7)2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35891464

RESUMEN

From 2010 to 2013, genotype I avian influenza A(H9N2) viruses of the G1-lineage were isolated from several poultry species in Egypt. In 2014, novel reassortant H9N2 viruses were detected in pigeons designated as genotype II. To monitor the subsequent genetic evolution of Egyptian A(H9N2) viruses, we characterized the full genomes of 173 viruses isolated through active surveillance from 2017 to 2022. In addition, we compared the virological characteristics and pathogenicity of representative viruses. Phylogenetic analysis of the HA indicated that all studied sequences from 2017-2021 were grouped into G1-like H9N2 viruses previously detected in Egypt. Phylogenetic analysis indicated that the Egyptian A(H9N2) viruses had undergone further reassortment, inheriting four genes (PB2, PB1, PA, NS) from genotype II, with their remaining segments deriving from genotype I viruses (these viruses designated as genotype III). Studying the virological features of the two most dominant genotypes (I and III) of Egyptian H9N2 viruses in vitro and in vivo indicated that both replicated well in mammalian cells, but did not show any clinical signs in chickens, ducks, and mice. Monitoring avian influenza viruses through surveillance programs and understanding the genetic and antigenic characteristics of circulating H9N2 viruses are essential for risk assessment and influenza pandemic preparedness.


Asunto(s)
Subtipo H9N2 del Virus de la Influenza A , Gripe Aviar , Gripe Humana , Animales , Pollos , Egipto/epidemiología , Humanos , Gripe Aviar/epidemiología , Mamíferos , Ratones , Filogenia , Virus Reordenados
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