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Structural basis of #receptor-binding #adaptation of #human-infecting #H3N8 #influenza A virus

ABSTRACT Recent avian-origin H3N8 influenza A virus (IAV) that have infected humans pose a potential public health concern . Alterations in the viral surface glycoprotein, hemagglutinin (HA), are typically required for IAVs to cross the species barrier for adaptation to a new host, but whether H3N8 has adapted to infect humans remains elusive. The observation of a degenerative codon in position 228 of HA in human H3N8 A/Henan/4-10/2022 protein sequence , which could be residue G or S, suggests a dynamic viral adaptation for human infection. Previously, we found this human-isolated virus has shown the ability to transmit between ferrets via respiratory droplets , with the HA-G228S substitution mutation emerging as a critical determinant for the airborne transmission of the virus in ferrets. Here, we investigated the receptor-binding properties of these two H3N8 HAs. Our results showed H3N8 HAs have dual receptor-binding properties with a preference for avian receptor binding , and G228S...

#Dynamics of a #Panzootic: Genomic #Insights, #Host Range, and #Epidemiology of the Highly Pathogenic Avian #Influenza A(#H5N1) Clade 2.3.4.4b in #USA

Abstract In late 2021, Eurasian-lineage highly pathogenic avian influenza (HPAI) A(H5N1) viruses from HA clade 2.3.4.4b were first detected in the United States . These viruses have caused severe morbidity and mortality in poultry and have been detected in numerous wild and domestic animals , including cows and humans . Notably, infected cows transmitted the virus to cats , causing extreme pathogenicity and death. While human-to-human spread of the virus has not been recorded, efficient transmission of the bovine-origin virus has also led to extreme pathogenicity and death in ferret models . Recently, markers in PB2 (E627K) and HA (E186D, Q222H), indicating mammalian adaptation mutations , were detected in an H5N1-infected patient manifesting critical illness in Canada . These, combined with instances of interspecies spread of the virus , have raised global public health concerns. This could highlight the potential for the virus to successfully adapt to mammals, posing a serious risk o...

#Efficacy and #safety of #sipavibart for #prevention of #COVID19 in individuals who are immunocompromised (SUPERNOVA)...

Summary Background Sipavibart is an anti-spike monoclonal antibody that neutralises SARS-CoV-2 with exceptions, including Phe456Leu-containing variants (eg, KP.2* and KP.3*). This trial assessed sipavibart efficacy and safety for prevention of symptomatic COVID-19 in participants who are immunocompromised. Methods In this ongoing, double-blind, international, phase 3 trial , we enrolled participants who were immunocompromised and aged 12 years or older at 197 hospitals, university health centres, and clinical trial units in 18 countries. Participants were randomly allocated 1:1 to a sipavibart group (intramuscular sipavibart 300 mg on days 1 and 181) or a comparator group (tixagevimab 300 mg–cilgavimab 300 mg on day 1 and placebo on day 181 or placebo on days 1 and 181), stratified by previous COVID-19 vaccination and infection status and use of tixagevimab–cilgavimab. The primary efficacy outcomes were symptomatic COVID-19 caused by any variant or symptomatic COVID-19 caused by non-Ph...

#Exposure and #survival of wild #raptors during the 2022–2023 highly pathogenic #influenza a virus #outbreak

Abstract The global outbreak of clade 2.3.4.4b H5N1 highly pathogenic influenza A virus (HP H5N1) has had an unprecedented impact on wild birds including raptors , but long-term population impacts have not been addressed. To determine if raptors survive infections with HP H5N1, raptors from the upper Midwest United States were serologically tested for antibodies to influenza A virus (IAV), H5 and N1. Raptors were sampled at The Raptor Center’s (University of Minnesota) wildlife rehabilitation hospital and at Hawk Ridge Bird Observatory. Samples were tested for IAV antibodies using a commercially available blocking ELISA, with positive samples tested for antibodies to H5 and N1. Antibodies to IAV were detected in 86 out of 316 individuals representing 7 species. Antibodies to H5 and N1 were detected in 60 individuals representing 6 species . Bald eagles had the highest seroprevalence with 67/97 (69.1%) seropositive for IAV and 52 of these 67 (77.6%) testing positive for antibodies to bo...

#Monkeypox Virus Occurrence in #Wastewater #Environment and Its Correlation with Incidence Cases of #Mpox: A Systematic Review and Meta-Analytic Study

Abstract The COVID-19 pandemic has increased the interest in the use of wastewater-based surveillance (WBS) strategy for infectious disease monitoring, especially when clinical cases are underreported. The excretion of monkey virus (MPXV) in the feces of both symptomatic and preclinical individuals has further driven the interest in WBS applicability to MPXV monitoring in wastewater to support its mitigation efforts. We performed a systematic review with meta-analysis, using six databases to assess MPXV detection in wastewater. We performed a random-effects model meta-analysis to calculate the pooled prevalence at a 95% confidence interval (95% CI). Also, we carried out a subgroup analysis according to the country regions and a sensitivity analysis excluding studies classified as having a high risk of bias. The overall MPXV positivity rate in wastewater was estimated at 22% (95% CI: 14−30%; I2 = 94.8%), with more detection rate in North America (26%, 95% CI: 8–43%) compared to Europe a...

The #Impact of Highly Pathogenic Avian #Influenza #H5N1 in the #USA: A Scoping #Review of Past #Detections and Present #Outbreaks

Abstract Highly Pathogenic Avian Influenza H5N1 (HPAI H5N1) was first detected in chickens in Scottland in 1959 and has since circulated globally, causing regular outbreaks among different animal species, as well as incidental infections in humans . In this scoping review, the epidemiology and impact of HPAI H5N1 among migratory birds, poultry, and cattle in the United States were analyzed, with a particular focus on outbreaks since January 2022. Following PRISMA guidelines, a total of 27 articles were identified for this review. Publicly available data and reports from the USDA and CDC were also evaluated and summarized. The identified articles primarily included epidemiological studies of detections in wild birds, mammals, and case reports on H5N1 and transmission dynamics among cattle , with a notable absence of poultry-focused reports . Wild birds, especially migratory species, have played an important role in virus dissemination. Studies among mammals , including seals, bears, and...

Highly Pathogenic Avian #Influenza A (#H5N1) Clade 2.3.2.1a virus #infection in domestic #cats, #India, 2025

Abstract In January 2025, the highly pathogenic avian influenza A(H5N1) virus clade 2.3.2.1a infection was detected in domestic cats and whole-genome sequencing of two cat H5N1 isolates was performed using the Oxford Nanopore MinION sequencing platform. Phylogenetic analysis revealed the circulation of triple reassortant viruses in cats. Although cat viruses lacked classic mammalian adaptation markers they carried mutations associated with enhanced polymerase activity in mammalian cells and increased affinity for α2-6 sialic acid receptor suggesting their potential role in facilitating infection in cats. The identification of reassortant HPAI H5N1 clade 2.3.2.1a viruses in domestic cats in India highlights the urgent need for enhanced surveillance in domestic poultry, wild birds, and mammals, including humans, to track genomic diversity and molecular evolution of circulating strains. Source: BioRxIV,  https://www.biorxiv.org/content/10.1101/2025.02.23.638954v1 ____

In-hospital #outcomes and 6-month follow-up results of #patients supported with #ECMO for #COVID19 from the 2nd wave to end of pandemic (EuroECMO-COVID)...

Summary Background Extracorporeal membrane oxygenation (ECMO) for COVID-19 was thoroughly assessed during the first pandemic wave , but data on subsequent waves are limited. We aimed to investigate in-hospital and 6-month survival of patients with COVID-19 supported with ECMO from the second pandemic wave (Sept 15, 2020) until the end of the pandemic (March 21, 2023, announced by WHO). Methods EuroECMO-COVID is a prospective, observational study including adults (aged ≥16 years) requiring ECMO respiratory support for COVID-19 from 98 centres in 21 countries. We compared patient characteristics and outcomes between in-hospital survivors and non-survivors. Mixed-effects multivariable logistic regressions were used to investigate factors linked to in-hospital mortality. 6-month survival and overall patient status were determined via patient contact or chart review. This study is registered with ClinicalTrials.gov, NCT04366921, and is complete. Findings We included 3860 patients (2687 [69·...

Structure-based #Design of Chimeric #Influenza #Hemagglutinins to Elicit Cross-group #Immunity

Abstract Antigenic variability among influenza virus strains poses a significant challenge to developing broadly protective , long-lasting vaccines . Current annual vaccines target specific strains, requiring accurate prediction for effective neutralization. Despite sequence diversity across phylogenetic groups, the hemagglutinin (HA) head domain's structure remains highly conserved. Utilizing this conservation, we designed cross-group chimeric HAs that combine antigenic surfaces from distant strains. By structure-guided transplantation of receptor-binding site (RBS) residues, we displayed an H3 RBS on an H1 HA scaffold . These chimeric immunogens elicit cross-group polyclonal responses capable of neutralizing both base and distal strains. Additionally, the chimeras integrate heterotrimeric immunogens, enhancing modular vaccine design. This approach enables the inclusion of diverse strain segments to generate broad polyclonal responses. In the future, such modular immunogens may se...

A Vestal Virgin Crowned With Flowers, Jacques-Louis David (1783)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/jacques-louis-david/a-vestal-virgin-crowned-with-flowers ____

#Coronavirus Disease Research #References (by AMEDEO, Feb. 23 '25)

  Antiviral Res INOUE A, Ichikawa T, Wada D, Maruyama S, et al M49L and other drug resistance mutations emerging in individuals after administration of ensitrelvir in Japanese clinical settings. Antiviral Res. 2025;236:106118. PubMed           Abstract available ZIAN D, Iaconis D, Nenci S, Crusco A, et al The Efficiency of High-Throughput Screening (HTS) and in-silico data analysis during medical emergencies: identification of effective antiviral 3CLpro inhibitors. Antiviral Res. 2025 Feb 18:106119. doi: 10.1016/j.antiviral.2025.106119. PubMed           Abstract available Clin Infect Dis LUETKEMEYER AF, Chew KW, Lacey S, Hughes MD, et al Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial. Clin Infect Dis. 2025 Feb 17:ciaf029. doi: 10.1093. PubMed       ...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Feb. 23 '25)

  Antiviral Res SCHREIBER A, Ludwig S Host-targeted antivirals against SARS-CoV-2 in clinical development - Prospect or disappointment? Antiviral Res. 2025;235:106101. PubMed           Abstract available WU Q, Wu H, Hu Y, Zheng X, et al Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients. Antiviral Res. 2025 Jan 24:106092. doi: 10.1016/j.antiviral.2025.106092. PubMed           Abstract available XU M, Zhang Z, Sun Y, Mai H, et al IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility. Antiviral Res. 2025 Jan 17:106082. doi: 10.1016/j.antiviral.2025.106082. PubMed           Abstract available Biochemistry LEE S, Yan S, Dey A, Laederach A, et al A Cascade of Conformational Switches in SARS-CoV-2 Frame...

#Genomics of novel #influenza A virus (#H18N12) in #bats, Caribe #Colombia

Abstract Influenza viruses are highly capable of mutating and adapting in mammalian hosts . While these viruses have been extensively studied in birds, research on their presence in bats has been limited. However, influenza viruses circulating in bats have shown notable molecular divergence . The present study aimed to characterize the phylogenetic, evolutionary, and antigenic relationships of an influenza A virus detected in the fishing bat Noctilio albiventris . As part of a pathogen surveillance study of public health interest, 159 rectal samples were collected from bats in the Colombian Caribbean . The samples were sequenced using RNA-Seq. A genome (eight viral contigs) associated with the Orthomyxoviridae family was identified in a pool. Most segments showed approximately 90% similarity with H18N11, except for the neuraminidase. Analysis of the N protein shows that occupies a basal position relative to the N11 subtype, with its divergence date estimated to be approximately 50 year...

A #framework for #tracking global #progress on #preparedness for #respiratory #pandemics

{Summary} 1 Introduction The COVID-19 pandemic underscored the urgency of ensuring that the world is prepared for the next major respiratory pathogen pandemic (1). Corresponding with World Health Assembly resolutions WHA58 .5 (2) and WHA74.7 (3), WHO is committed to supporting Member States with pandemic preparedness planning through the provision of guidance and technical assistance . Following on from the PRET Global Meeting in April 2023, WHO has finalized guidance on Preparedness and resilience for emerging threats (PRET) module (1): planning for respiratory pathogen pandemics. This module acknowledges that similar systems and capacities can be used to prevent, prepare for and respond to different respiratory pathogens. The module (4) has three overarching objectives: - to guide countries and partners in developing or updating their integrated approach to respiratory pathogen pandemic preparedness for equitable and robust response; - to focus attention on the actions needed to stre...

Genetic Diversity and #Geographic #Spread of #Henipaviruses

Abstract Henipaviruses, such as Hendra and Nipah viruses, are major zoonotic pathogens that cause encephalitis and respiratory infections in humans and animals . The recent emergence of Langya virus in China highlights the need to understand henipavirus host diversity and geographic spread to prevent future outbreaks. Our analysis of the National Center for Biotechnology Information Virus and VIRION databases revealed ≈1,117 henipavirus sequences and 142 complete genomes. Bats (64.7%) and shrews (11.7%) dominated the host species record, and the genera Pteropus and Crocidura contained key henipavirus hosts in Asia, Australia, and Africa . Henipaviruses found in the Eidolon bat genus exhibited the highest within-host genetic distance. Phylogenetic analysis revealed batborne and rodent- or shrew-derived henipaviruses diverged ≈11,000 years ago and the first known lineage originating in Eidolon genus bats ≈9,900 years ago. Pathogenic henipaviruses diverged from their ancestors 2,800–1,200...

Effect of Prior #Influenza #H1N1pdm09 Virus #Infection on #Pathogenesis and #Transmission of #Human Influenza A(#H5N1) Clade 2.3.4.4b Virus in #Ferret Model

Abstract Reports of human infections with an influenza A(H5N1) clade 2.3.4.4b virus associated with outbreaks in dairy cows in the United States underscore the need to assess the potential cross-protection conferred by existing influenza immunity . We serologically evaluated ferrets previously infected with an influenza A(H1N1)pdm09 virus for cross-reactive antibodies and then challenged 3 months later with either highly pathogenic H5N1 clade 2.3.4.4b or low pathogenicity H7N9 virus . Our results showed that prior influenza A(H1N1)pdm09 virus infection more effectively reduced the replication and transmission of the H5N1 virus than did the H7N9 virus, a finding supported by the presence of group 1 hemagglutinin stalk and N1 neuraminidase antibodies in preimmune ferrets. Our findings suggest that prior influenza A(H1N1)pdm09 virus infection may confer some level of protection against influenza A(H5N1) clade 2.3.4.4.b virus. Source: US Centers for Disease Control and Prevention,  htt...

#Influenza A(#H5N1) Immune #Response among #Ferrets with Influenza #H1N1pdm09 #Immunity

Abstract The emergence of highly pathogenic avian influenza A(H5N1) virus in dairy cattle herds across the United States in 2024 caused several human infections . Understanding the risk for spillover infections into humans is crucial for protecting public health. We investigated whether immunity from influenza A(H1N1)pdm09 (pH1N1) virus would provide protection from death and severe clinical disease among ferrets intranasally infected with H5N1 virus from dairy cows from the 2024 outbreak. We observed differential tissue tropism among pH1N1-immune ferrets. pH1N1-immune ferrets also had little H5N1 viral dissemination to organs outside the respiratory tract and much less H5N1 virus in nasal secretions and the respiratory tract than naive ferrets. In addition, ferrets with pH1N1 immunity produced antibodies that cross-reacted with H5N1 neuraminidase protein. Taken together, our results suggest that humans with immunity to human seasonal influenza viruses may experience milder disease fro...

Urban #Coatis (Nasua nasua) Exposure to #Alphainfluenzavirus influenzae

Abstract We detected neutralizing antibodies, viral RNA, and sialic acid receptors for Alphainfluenzavirus influenzae in urban coatis (Nasua nasua) in Brazil , suggesting exposure and susceptibility. We used hemagglutination inhibition, reverse transcription qualitative PCR, and immunohistochemistry for detection. Increased epidemiologic wildlife surveillance would improve influenza A emergency event response. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/3/23-1640_article ____

#Human #Infection with Avian #Influenza A(#H9N2) Virus, #Vietnam, April 2024

Abstract In April 2024, Vietnam confirmed its first human case of influenza A(H9N2) in a 37-year-old man , marking a critical point in regional infectious disease monitoring and response. This case underscores the importance of robust surveillance systems and One Health collaboration in managing emerging zoonotic threats. Source: Emerging Infectious Diseases Journal,  https://wwwnc.cdc.gov/eid/article/31/2/24-1146_article ____

#Sudan virus #disease - #Uganda

{Excerpt} Situation at a glance As of 20 February 2025, a total of nine confirmed cases of Sudan virus disease, including one death have been reported from Uganda , since the outbreak was declared on 30 January 2025. Eight cases received care at treatment centres in the capital Kampala and in Mbale and were discharged on 18 February after two negative tests 72 hours apart.  As of 20 February 2025, 58 contacts that have been identified are still under follow up in designated quarantine facilities located in Jinja, Kampala,and Mbale .  Sudan virus disease belongs to the same family as Ebola virus disease . It is caused by Sudan virus (SUDV). It is a severe disease with high case fatality ranging from 41% to 70% in past outbreaks. In the absence of licensed vaccines and therapeutics for the prevention and treatment of SVD, the risk of potential serious public health impact is high. Early detection, diagnosis, and optimized supportive care may increase the chance of survival. Desc...