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Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry across Asia, Europe, and Africa. By the end of 2021, 2.3.4.4b viruses were detected in North America, signifying further intercontinental spread. Here we show that the western movement of clade 2.3.4.4b was quickly followed by reassortment with viruses circulating in wild birds in North America, resulting in the acquisition of different combinations of ribonucleoprotein genes. These reassortant A(H5N1) viruses are genotypically and phenotypically diverse, with many causing severe disease with dramatic neurologic involvement in mammals. The proclivity of the current A(H5N1) 2.3.4.4b virus lineage to reassort and target the central nervous system warrants concerted planning to combat the spread and evolution of the virus within the continent and to mitigate the impact of a potential influenza pandemic that could originate from similar A(H5N1) reassortants. Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry. Here, Kandeil et al. show that the Western movement of this clade was followed by reassortment with viruses circulating in wild birds in North America which resulted in different genotypes exhibiting a wide range of disease severity in mammal models (mice, ferrets, chicken) ranging from asymptomatic disease to severe neurological pathology.

The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern 1 – 4 . Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral entry, raising concerns that the replication capacity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here we have evaluated the replicative ability and pathogenicity of BA.4 and BA.5 isolates in wild-type Syrian hamsters, human ACE2 (hACE2) transgenic hamsters and hACE2 transgenic mice. We have observed no obvious differences among BA.2, BA.4 and BA.5 isolates in growth ability or pathogenicity in rodent models, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 clinical isolates have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2. Results indicate that the sublineages BA.4 and BA.5 of SARS-CoV-2 Omicron variants have similar pathogenicity to that of the BA.2 sublineage in rodents, highlighting the importance of evaluating viral replication and pathogenesis using clinical isolates.

During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many of the FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro and remarkable efficacy against COVID-19 in clinical trials, no pharmaceutical products have yet been declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes for the treatment of depression, neuralgia, migraine prophylaxis, and eating disorders which are frequently reported symptoms in COVID-19 patients. Herein, the efficacy of eight frequently prescribed FDA-approved antidepressants on the inhibition of both SARS-CoV-2 and MERS-CoV was assessed. Additionally, the in vitro anti-SARS-CoV-2 and anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies have been performed for these drugs against the spike (S) and main protease (M pro ) pockets of both SARS-CoV-2 and MERS-CoV. Results showed that Amitriptyline, Imipramine, Paroxetine, and Sertraline had potential anti-viral activities. Our findings suggested that the aforementioned drugs deserve more in vitro and in vivo studies targeting COVID-19 especially for those patients suffering from depression.

Introduction Two years after unprecedented low rates of circulation of most common respiratory viruses (SARS-CoV-2), the Egyptian ARI surveillance system detected an increase in acute respiratory infections (ARIs) with a reduced circulation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially among school children. A national survey was conducted to estimate the burden and identify the viral causes of ARIs among children < 16 years of age. Methods A one-day survey was carried out in 98 governmental outpatient clinics distributed all over Egypt 26 governorates. The four largest referral hospitals in each governorate where most influenza-like illness (ILI) patients seek care were selected. Using the WHO case definition, the first five patients < 16 years of age with ILI symptoms visiting the selected outpatient clinics on the survey day were enrolled. Basic demographic and clinical data of patients were collected using a linelist. Patients were swabbed and tested for SARS-CoV-2, influenza, and Respiratory Syncytial virus (RSV) by RT-PCR at the Central Laboratory in Cairo. Results Overall, 530 patients enrolled, their mean age was 5.8 ± 4.2, 57.1% were males, and 70.2% reside in rural or semi-rural areas. Of all patients, 134 (25.3%) had influenza, 111 (20.9%) RSV, and 14 (2.8%) coinfections. Influenza-positive children were older compared to RSV, (7.2 ± 4.1, 4.3 ± 4.1, p < 0.001), with more than half of them (53.0%) being school students. Dyspnea was reported in RSV more than in influenza (62.2% vs. 49.3%, p < 0.05). Among RSV patients, children < 2 years had a higher rate of dyspnea than others (86.7% vs. 53.1%, < 0.001). Conclusions A resurgence of influenza and RSV was detected in Egypt in the 2022–2023 winter season. Influenza caused a higher rate of infection than RSV, while RSV caused more severe symptoms than influenza. Monitoring a broader range of respiratory pathogens is recommended to estimate the ARI burden and risky groups for severe disease in Egypt.

(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.

Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures. We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir, the polymerase inhibitors baloxavir and favipiravir, and an ion-channel blocker amantadine, against severe influenza A(H5N1) virus infection in female BALB/c mice. Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death, significantly reduced virus respiratory replication, and prevented neuroinvasion. Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits, reduced lung titers but failed to prevent viral neuroinvasion. Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection, although did not reduce viral titers in lungs and brain. Amantadine provided no benefits. Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir. Our results indicate that baloxavir is the most reliable treatment to address both respiratory replication and systemic spread of contemporary A(H5N1) viruses in mice and should be considered in pandemic planning. Here the authors assess baloxavir, oseltamivir, favipiravir, or amantadine for treatment of severe influenza A(H5N1) in female mice and find that baloxavir provides best survival outcomes with reduced lung replication and viral neuroinvasion, supporting its consideration for use in human A(H5N1) infections.

Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kβ p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kβ/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kβ pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.

Until now, there has been no direct evidence of the effectiveness of repurposed FDA-approved drugs against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections. Although curcumin, hesperidin, and quercetin have broad spectra of pharmacological properties, their antiviral activities against SARS-CoV-2 remain unclear. Our study aimed to assess the in vitro antiviral activities of curcumin, hesperidin, and quercetin against SARS-CoV-2 compared to hydroxychloroquine and determine their mode of action. In Vero E6 cells, these compounds significantly inhibited virus replication, mainly as virucidal agents primarily indicating their potential activity at the early stage of viral infection. To investigate the mechanism of action of the tested compounds, molecular docking studies were carried out against both SARS-CoV-2 spike (S) and main protease (Mpro) receptors. Collectively, the obtained in silico and in vitro findings suggest that the compounds could be promising SARS-CoV-2 Mpro inhibitors. We recommend further preclinical and clinical studies on the studied compounds to find a potential therapeutic targeting COVID-19 in the near future.

The zoonotic origin of the COVID-19 pandemic virus highlights the need to fill the vast gaps in our knowledge of SARS-CoV-2 ecology and evolution in non-human hosts. Here, we detected that SARS-CoV-2 was introduced from humans into white-tailed deer more than 30 times in Ohio, USA during November 2021-March 2022. Subsequently, deer-to-deer transmission persisted for 2–8 months, disseminating across hundreds of kilometers. Newly developed Bayesian phylogenetic methods quantified how SARS-CoV-2 evolution is not only three-times faster in white-tailed deer compared to the rate observed in humans but also driven by different mutational biases and selection pressures. The long-term effect of this accelerated evolutionary rate remains to be seen as no critical phenotypic changes were observed in our animal models using white-tailed deer origin viruses. Still, SARS-CoV-2 has transmitted in white-tailed deer populations for a relatively short duration, and the risk of future changes may have serious consequences for humans and livestock. White-tailed deer are an important reservoir of SARS-CoV-2 in the USA and continued monitoring of the virus in deer populations is needed. In this genomic epidemiology study from Ohio, the authors show that the virus has been introduced multiple times to deer from humans, and that it has evolved faster in deer.

Highly pathogenic avian influenza (HPAI) viruses have recently had a substantial impact on global poultry production and public health. In Egypt, clade 2.3.4.4b HPAI H5N1 viruses were first isolated from wild birds in 2021 and then became dominant in domestic poultry. In this study, we aimed to genetically characterize the H5N1 viruses isolated in Egypt during 2021–2023 and examine the pathogenicity and transmissibility of two H5N1 strains isolated from wild and domestic poultry in chickens. We collected 7588 specimens from live bird markets including poultry, wild birds, and environmental samples. Influenza A viruses were detected in 20.94% (484/2311) of tested samples, and 17 isolates were identified as H5N1 through complete genome sequencing. Phylogenetic analysis revealed that all H5N1 viruses were closely related to Eurasian viruses and classified into three distinct genetic groups, suggesting multiple introductions likely linked to migratory birds. Experimental infections of chickens with two H5N1 isolates, A/Pintail/Egypt/RA19853OP/2021 and A/duck/Egypt/BA20361C/2022, showed efficient replication, systemic infection, and transmission by direct contact. These findings underscore the need for continued surveillance of H5N1 at the poultry-wild bird interface to identify circulating strains, evaluate their biological characteristics, and assess their zoonotic potential.