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Molecular basis of #influenza #ribonucleoprotein complex #assembly and processive #RNA synthesis

Abstract Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex . By integrating cryo–electron microscopy single-particle analysis and cryo–electron tomography , we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove . Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states , revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors . These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development. Source: Science,  https://www.science.org/doi/10.1126/science...

#Statement on the #antigen #composition of #COVID19 #vaccines (#WHO, May 15 '25)

  Key points -- Vaccination remains an important public health countermeasure against COVID-19 . As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE). -- SARS-CoV-2 continues to undergo sustained evolution since its emergence in humans, with important genetic and antigenic changes in the spike protein. -- The objective of an update to COVID-19 vaccine antigen composition is to enhance vaccine-induced immune responses to circulating SARS-CoV-2 variants. -- The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) advises manufacturers that monovalent JN.1 or KP.2 vaccines remain appropriate vaccine antigens ; monovalent LP.8.1 is a suitable alternative vaccine antigen . -- In accordance with WHO SAGE policy, vaccination should not be delayed in anticipation of access to vacci...

Genetic diversity of #H5N1 avian #influenza viruses isolated from #birds and #seals in #Russia in 2023

Abstract Thousands of outbreaks of the highly pathogenic avian influenza A(H5N1) virus in birds and an increasing number of mammal infections are registered annually. In 2023, multiple avian influenza outbreaks were registered among wild birds, poultry and seals in Russia . The genetic characterization of seventy-seven avian viruses and three viruses from seals showed that they belonged to the 2.3.4.4b clade and represented four distinct reassortant genotypes . The majority of viruses represented genotype BB , which was widespread in Europe in 2023. Viruses from seals and four viruses from birds , isolated from outbreaks in the Far East region , belonged to the G1 (A3) genotype and had the amino acid substitution N319K in the NP protein , previously associated with an increased virulence for mammals . In addition, one virus of the G10 genotype and two viruses, representing a previously undescribed genotype (designated as Ru-23-G4) were identified. The viruses analyzed showed normal inh...

#Investigation of #Influenza #H5N1 Virus #Neutralization by Quadrivalent Seasonal #Vaccines, #UK, 2021–2024

Abstract We tested cross-neutralization against highly pathogenic avian influenza A(H5N1) virus in adults vaccinated with 2021–2023 seasonal quadrivalent influenza vaccine in the United Kingdom. Seasonal quadrivalent influenza vaccines are unlikely to protect vulnerable persons against severe H5N1 disease during widespread transmission. Enhanced measures are needed to protect vulnerable people from H5N1 virus infection. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/6/24-1796_article ____

Emergence of #Antigenic #Variants in #Bovine #H5N1 #Influenza Viruses

ABSTRACT The recent emergence of the H5N1 influenza virus in dairy cattle has raised significant public health concerns . Using a previously established pseudovirus-based neutralization assay , we evaluated the impact of emerging hemagglutinin (HA) mutations on the efficacy of current candidate vaccine viruses (CVVs). Neutralization analysis revealed that the cow-derived H5N1 virus showed up to a 2.2-fold reduction in sensitivity compared to the CVV homologous neutralization titers. Among the 1,453 HA sequences analyzed from cow-derived H5N1 viruses, we identified four major mutations (E2K, D104G, V147M, and S336N) that emerged after the initial isolation, with 134 isolates (9.22%) harboring all four mutations . These multi-mutation variants exhibited up to a 3.3-fold reduction compared with the CVV homologous neutralization titers. Single-mutation analysis demonstrated that the D104G mutation , present in 47.8% of sequences, markedly contributed to antibody escape . Our findings highl...

Effects of #JAK #inhibitors in adults admitted to #hospital due to #COVID19: a systematic review and individual participant data meta-analysis of randomised clinical trials

Summary Background Evidence from randomised clinical trials (RCTs) of Janus kinase (JAK) inhibitors —compared with usual care or placebo—in adults treated in hospital for COVID-19 is conflicting. We aimed to evaluate the benefits and harms of JAK inhibitors compared with placebo or usual care and whether treatment effects differed between prespecified participant subgroups. Methods For this systematic review and individual participant data meta-analysis (IPDMA), we searched Medline via Ovid, Embase via Elsevier, the Cochrane Central Register of Controlled Trials , the Cochrane COVID-19 Study Register, and the COVID-19 L·OVE Platform, including backward and forward citation searching (last search Nov 28, 2024), for RCTs (unpublished or published in any format and any language) that randomly assigned adults (aged ≥16 years) admitted to a hospital due to COVID-19 to receive either a JAK inhibitor (any type) or no JAK inhibitor (ie, received site-specific standard of care with or without p...

#Measles - #Morocco (#WHO D.O.N., May 13 '25)

{Summary} Situation at a glance Since late 2023, Morocco has been experiencing a widespread measles outbreak . Cases have been recorded across all regions of the country, particularly among children and people who are unvaccinated . In response, the Ministry of Health and Social Protection (MOHSP), in collaboration with relevant sectors, activated the National Center for Public Health Emergency Operations , launched urgent catch-up vaccination campaigns , and strengthened surveillance, case management, and risk communication and community engagement efforts. Measles is a highly transmissible viral disease that can lead to severe complications and death. While Morocco has made significant progress toward measles elimination, the disease remains endemic in the country. The overall risk is assessed as moderate at the national level and moderate at the regional level , particularly given the risk of cross-border transmission in areas with low vaccination coverage. (...) Source: World Healt...

#China reported eight new #human cases of #Influenza A #H9N2 and one new case of Influenza A #H10N3 (HK CHP, May 13 '25)

  {Excerpt} Avian influenza A(H9N2) :  -- New Cases (New Deaths): 8 (0)  - Chongqing Municipality :  - 1) A 67-year-old man with onset on April 18, 2025.  - Guizhou Province :  - 2)  A one-year-old girl with onset on April 7, 2025.  - 3) A one-year-old girl with onset on April 15, 2025.  - Hunan Province :  - 4) A five-year-old boy with onset on April 1, 2025. - 5) A seven-year-old girl with onset on April 1, 2025.  - 6) A one-year-old girl with onset on April 3, 2025.  - 7) A five-year-old boy with onset on April 19, 2025 - Yunnan Province : - 8) A one-year-old girl with onset on April 2, 2025 Avian influenza A(H10N3) :  - Guangxi Zhuang Autonomous Region :  - 1) A 68-year-old woman with onset on April 13, 2025.  (...) Source: Centre for Health Protection, Hong Kong PRC SAR,  https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk19.pdf ____

#Philippines - High pathogenicity avian #influenza #H5N9 viruses (#poultry) (Inf. with) - Immediate notification

The affected population are ducks grazing in a rice field situated within Camaligan, Camarines Sur where they may have come into contact with wild birds carrying the virus. Source: WOAH,  https://wahis.woah.org/#/in-review/6473 ____

Effectiveness of integrated #vector #management on the incidence of #dengue in urban #Malaysia: a cluster-randomised controlled trial

Summary Background Malaysia is one of the southeast Asian countries hardest hit by dengue . We implemented a proactive integrated vector management (IVM) approach in a large non-blinded, cluster-randomised controlled trial to quantify its effectiveness on dengue incidence in urban settings. Methods In this cluster-randomised controlled trial we enrolled low-cost and medium-cost residential housing blocks in the Federal Territory of Kuala Lumpur and Putrajaya with recurrent dengue outbreaks. Of the 329 eligible sites, 139 were randomly allocated to receive IVM measures (community engagement, targeted outdoor residual spraying using K-Othrine Polyzone , and deployment of autodissemination devices to target both larval and adult mosquitoes) and 141 received routine vector control activities, stratified by block housing cost. The primary outcome was the comparison of dengue incidence between the two groups using information provided by the national e-Dengue surveillance system. Routine vec...

Dose response comparison of #Nipah virus #strains #Malaysia and #Bangladesh in #hamsters exposed by the intranasal or intraperitoneal route

Abstract Nipah virus, a zoonotic pathogen, can cause debilitating disease and death in humans. Currently, countermeasures are limited , with several in various stages of testing but none yet FDA-approved for human use. Evaluation of countermeasure candidates requires safety testing in humans, as well as efficacy testing against lethal challenge in animal models . Herein, we describe the characterization and comparison of the intraperitoneal and intranasal Syrian golden hamster models for Nipah virus strains Malaysia and Bangladesh . Overall, the intraperitoneal route of exposure resulted in a more consistent lethal outcome, regardless of virus strain. Therefore, the IP model was subsequently used to evaluate the use of Favipiravir as a potential positive control for future studies investigating NiV countermeasures. In contrast to prior reported results regarding Favipiravir in Nipah virus-infected hamsters, Favipiravir was only fifty percent effective at preventing death following leth...

Pregnant Dairy #Heifers Express #Influenza A Virus #Receptors in the Mammary #Gland

Abstract Highly pathogenic avian influenza (HPAI) A(H5N1) virus emerged in lactating dairy cattle in March 2024, causing mastitis-related disease and infections in other farm animals and workers . Recent work identified α2,6 and α2,3-linked sialic acids (SA), which serve as influenza virus receptors, in the lactating bovine mammary gland ; however, their distribution across stages of mammary growth and development remains unknown. We compared the distribution of tissue sialylation in mammary glands of prepubertal dairy calves , pregnant dairy heifers , and lactating cows . Mammary glands at all physiological stages expressed both α2,6 SA, the preferred receptor linkage for human influenza viruses, and α2,3 SA, the preferred receptor linkage for avian influenza viruses. Importantly, mammary glands of pregnant dairy heifers exhibited the highest overall expression of α2,3 SA, observed in both tissue and alveolar lumens. Our results suggest that pregnant dairy heifers, like lactating dair...

Clade 2.3.4.4b Highly pathogenic #H5N1 #influenza viruses from #birds in #China replicate effectively in #bovine cells and pose potential public health #risk

Abstract In February 2024, H5N1 highly pathogenic avian influenza viruses (HPAIVs) of clade 2.3.4.4b were first reported in dairy cows in the USA. Subsequent multiple outbreaks on dairy farms and sporadic human infections have raised substantial public health concerns . In the same year, four H5N1 HPAIVs of clade 2.3.4.4b were isolated from ducks and geese in live poultry markets (LPMs) spanning seven provinces in China . Evolutionary analysis demonstrated that these viruses had undergone two genetic reassortments with H5 influenza viruses from wild birds in different countries. Except for 565/H5N1, the other three viruses exhibited over 99% genetic homology with avian-origin H5N1 HPAIVs from South Korea and Japan . Notably, 571/H5N1 demonstrated high replication efficiency in bovine-derived cells , particularly in bovine mammary epithelial (MAC-T) cells, and caused 16.7% (1/6) mortality in mice at a dose of 10⁵ EID₅₀/50 μL, indicating its zoonotic potential . Given the potential cross...

Middle East respiratory syndrome #coronavirus {#MERS-CoV} - Kingdom of #Saudi Arabia (#WHO D.O.N., May 12 '25)

Situation at a glance Between 1 March and 21 April 2025, the Ministry of Health (MoH) of the Kingdom of Saudi Arabia (KSA) reported nine cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection . Two of these cases died . Among the nine cases, a cluster of seven cases were identified in Riyadh , including six health and care workers who acquired the infection from caring for a single infected patient . The cluster was identified through contact tracing and subsequent testing of all contacts, with four of the six health and care workers being asymptomatic and two showing only mild , nonspecific signs. The notification of these cases does not change the overall risk assessment , which remains moderate at both the global and regional levels. These cases show that the virus continues to pose a threat in countries where it is circulating in dromedary camels and spilling over into the human population . WHO recommends implementation of targeted infection prevention and cont...

#Pathogenesis Induced by #Influenza Virus #Infection: Role of the Early Events of the Infection and the Innate Immune Response

Abstract Infections by influenza A virus (IAV) are a significant cause of global mortality . The pathogenesis of the infection is usually studied in terms of direct viral-induced damage or the overreactive immune response that continues after the virus is cleared. However, factors such as the initial infectious dose , the early response after infection in different cell types, and the presence of autoantibodies for relevant antiviral cytokines like type I IFNs seem to influence the course of the infection and lead to fatal outcomes . In this article, we address the current knowledge about the early events during influenza virus infection, which are important for their participation in influenza-derived pathogenesis. Source: Viruses,  https://www.mdpi.com/1999-4915/17/5/694 ____

Identification & #genetic & #virological characterisation of a #human case of avian #influenza A #H9N2 virus from Eastern #India

Abstract Background & objectives A three-year-old male child from West Bengal, India , with severe acute respiratory symptoms , was confirmed in the laboratory with LPAI H9N2 virus infection under the Indian Council of Medical Research (ICMR) - Pan India Acute Respiratory Infections (ARI) / Severe Acute Respiratory Infections (SARI) surveillance through the Virus Research and Diagnostic Laboratories network. Methods Common respiratory viruses were detected by real-time PCR, followed by subtyping of Influenza A for seasonal and avian viruses. The identified H9N2 virus was isolated and further characterised, including whole genome sequencing. Antibody response was performed in serum samples of the case and family members. Results Complete genome sequencing revealed a G1 lineage (Middle East B sub-lineage). Bayesian evolutionary analyses of the HA gene of Indian H9N2 poultry strains showed three clusters of multiple introductions at the estimated node age of 1999 based on the Human st...

A Lady Standing at a Virginal, Johannes Vermeer (c.1670 - c.1672)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/johannes-vermeer/a-lady-standing-at-a-virginal ____

#Statement of the 41rst #meeting of the #Polio #IHR Emergency #Committee (#WHO, May 11 '25)

{Excerpts} The 41st meeting of the Emergency Committee under the International Health Regulations (2005) (IHR) on the international spread of poliovirus was convened by the WHO Director-General on 6 March 2025 with committee members and advisers meeting via video conference with affected countries, supported by the WHO Secretariat.   The Emergency Committee reviewed the data on wild poliovirus (WPV1) and circulating vaccine derived polioviruses (cVDPV) in the context of the global target of interruption and certification of WPV1 eradication by 2027 and interruption and certification of cVDPV2 elimination by 2029.  Technical updates were received about the situation in the following countries:  - Afghanistan,  - Algeria,  - Chad,  - Democratic Republic of the Congo (DR Congo),  - Djibouti,  - Ethiopia,  - Germany,  - Pakistan,  - Poland and  - the United Kingdom of Great Britain and Northern Ireland. (...) Based on the curr...

History of Mass Transportation: The FS ALn 556 Autorail

  Di B.Zsolt - Opera propria, CC BY-SA 3.0 , source: WikiPedia. ____

#Coronavirus Disease Research #References (by AMEDEO, May 10 '25)

  Antiviral Res MARTIN HJ, Hossain MA, Wellnitz J, Kelestemur E, et al Chemical arsenal for helicase Hunters: Striking the toughest targets in antiviral research. Antiviral Res. 2025;239:106184. PubMed           Abstract available Int J Infect Dis BANHOLZER N, Middelkoop K, Schmutz R, Leukes J, et al Infection prevention and control measures during the COVID-19 pandemic and airborne tuberculosis transmission during primary care visits in South Africa. Int J Infect Dis. 2025 May 6:107921. doi: 10.1016/j.ijid.2025.107921. PubMed           Abstract available J Infect RIEDMANN U, Chalupka A, Richter L, Werber D, et al Underlying health biases in previously-infected SARS-CoV-2 vaccination recipients: a cohort study. J Infect. 2025 Apr 30:106497. doi: 10.1016/j.jinf.2025.106497. PubMed           Abstract available J Med Virol MAZZOTTA V, Lepri AC, Del Borgo C, Lanini S,...