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#Molnupiravir clinical trial simulation suggests that #PCR underestimates #antiviral #potency against #SARS-CoV-2

  Abstract Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication . Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes . Model simulations suggested lower antiviral potency against pre-Omicron SARS-CoV-2 variants than against Omicron . We estimated that in vitro assays underestimated in vivo potency by 6- to 7-fold against Omicron variants. Our model suggested that because polymerase chain reaction detects molnupiravir mutated variants, the true reduction in non-mutated viral RNA was underestimated by approximately 0.4 log10 in the two trials conducted while Omicron variants dominated. Viral area under the curve estimates differed significantly between non-mutated and mutated viral RNA. Our results reinforce past work suggesting that in...

#Germany - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

  A laying hens farm in Sachsen-Anhalt Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6966 ____

#Romania - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

  {Di Sanchezn - Opera propria, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3019282 } Confirmation of HPAI - H5N1 case, at Cygnus olor Port Contanta Dana 55 in the Constanta county. Source: WOAH,  https://wahis.woah.org/#/in-review/6968 ____

A #cattle-derived #human #H5N1 isolate suppresses innate #immunity despite efficient #replication in human respiratory #organoids

  Abstract The H5N1 high pathogenicity avian influenza virus (HPAIV) of clade 2.3.4.4b, which spreads globally via wild birds , has become a major public health concern because it can infect a variety of mammals , including humans . In 2024, infection of dairy cattle with H5N1 HPAIV clade 2.3.4.4b was confirmed in the United States , and subsequent human cases were reported. Although these viruses are highly pathogenic in animal models , human infections have generally been mild , revealing a striking discrepancy . Here, we characterized the cattle-derived human H5N1 isolate A/Texas/37/2024 (TX37-H5N1) using three-dimensional human respiratory organoids derived from induced pluripotent stem (iPS) cells. Despite efficient replication , TX37-H5N1 induced minimal interferon and inflammatory cytokine responses . Bulk and single-cell RNA sequencing revealed reduced STAT1-mediated transcriptional activity in TX37-H5N1-infected organoids compared to the historic H5N1 human isolate A/Vietn...

The Nightmare (1781), Detroit Institute of Arts (Henry Fuseli)

  By Tulip Hysteria / Go to albums - https://www.flickr.com/photos/36417567@N03/32380012237/ , CC BY 2.5,  https://commons.wikimedia.org/w/index.php?curid=111521078 Source: Wikipedia,  https://en.wikipedia.org/wiki/Henry_Fuseli ____

HKU25 clade #MERS-related #coronaviruses use #ACE2 as a functional #receptor

  Abstract Dipeptidyl peptidase-4 (DPP4) is an established receptor for Middle East respiratory syndrome-related coronaviruses (MERSr-CoVs), while recent studies have identified angiotensin-converting enzyme 2 (ACE2) usage in multiple merbecovirus clades . Yet, receptor usage of many genetically diverse bat MERSr-CoVs remains unclear . Here we show that broadly distributed HKU25 clade merbecoviruses use ACE2 , rather than DPP4, as their receptor. Cryo-electron microscopy revealed that HsItaly2011 and VsCoV-a7 strains engage ACE2 similarly to HKU5 but with remodelled interfaces and distinct orthologue selectivity, suggesting a shared evolutionary origin of ACE2 recognition . EjCoV-3, a close relative of the DPP4-using BtCoV422, showed broad multi-species ACE2 tropism and preadaptation to human ACE2 . Several ACE2 glycans and residues within or near the binding interface were identified as determinants of orthologue selectivity. These viruses remain sensitive to several broadly neutr...

History of Mass Transportation: The Renault Autorail ABJ4 SNCF X 3600

  Par Original téléversé par Cheminot sur Wikipédia français. — Transféré de fr.wikipedia à Commons par Bloody-libu utilisant CommonsHelper., GPL,  https://commons.wikimedia.org/w/index.php?curid=16780226 Source: Wikipedia,  https://fr.wikipedia.org/wiki/Autorail_Renault ____

#Coronavirus Disease Research #References (by AMEDEO, October 1 '25)

  Clin Infect Dis CALABRESE C, Wang Y, Duggal A, Huang S, et al Effectiveness of Nirmatrelvir/Ritonavir or Molnupiravir Use in Immunocompromised Patients on B-Cell-Depleting Therapy With COVID-19: A Target Trial Emulation Study. Clin Infect Dis. 2025 Oct 24:ciaf521. doi: 10.1093. PubMed           Abstract available FONG Y, Huang Y, Huang Y, Woo W, et al Analysis of antibody markers as immune correlates of risk of severe COVID-19 in the PREVENT-19 efficacy trial of the NVX-CoV2373 recombinant protein vaccine. Clin Infect Dis. 2025 Oct 25:ciaf558. doi: 10.1093. PubMed           Abstract available KABORE JL, Laffont B, Diop M, Tardif MR, et al Real-World Effectiveness of Nirmatrelvir-Ritonavir in Preventing Coronavirus Disease 2019-Associated Hospitalization: A Population-Based Cohort Study in the Province of Quebec, Canada. Clin Infect Dis. 2025 Oct 29:ciaf145. doi: 10.1093. PubMed    ...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, October 1 '25)

  Arch Virol YIN Y, Chen J, Chen S, Huang J, et al The SARS-CoV-2 N protein disrupts G3BP1 function and alters lipid metabolism in COVID-19 pathogenesis. Arch Virol. 2025;170:237. PubMed           Abstract available Biochem Soc Trans CALL MJ, Call ME, Wu X Insights from deep mutational scanning in the context of an emerging pathogen. Biochem Soc Trans. 2025;53:1169-1179. PubMed           Abstract available BMC Pediatr VASQUEZ-LOARTE T, Guerra GA, Saldarriaga EM, Torres-Gomez L, et al Healthcare access satisfaction before and during the COVID-19 pandemic among Peruvian children with down syndrome. BMC Pediatr. 2025;25:874. PubMed           Abstract available Drugs SYED YY Clesrovimab: First Approval. Drugs. 2025;85:1487-1492. PubMed           Abstract available J Exp Med BISSETT C, Yong L, Spencer AJ, Ma FNL, et al Heterologo...

History of Mass Transportation: The Brissonneau et Lotz D7122 Diesel Locomotive

  By CARLOS TEIXIDOR CADENAS - Own work, CC BY-SA 4.0,  https://commons.wikimedia.org/w/index.php?curid=54505585 Source: WikiMedia Commons,  https://commons.wikimedia.org/wiki/File:Alameda_o_Estaci%C3%B3n_Central_de_Santiago_de_Chile,_con_el_Tren_del_Recuerdo_a_la_derecha.jpg ____

#Italy, #WNV & #USUV Integrated #Surveillance - Weekly Bulletin No. 16 - 30 October 2025 (Summary)

  {Summary} -- During current epidemiological week (from  23 to 29 Oct. 2025) , two new human cases of infection with West Nile Virus have been reported.  -- The cumulative number of confirmed cases this season so far rose to 773 (they were 771 last week), of these:  - 367 were West Nile Neuroinvasive Disease (WNND): 17 in Piedmont, 56 Lombardy, 35 Veneto, 4 Friuli-Venezia Giulia, 1 Liguria, 30 Emilia-Romagna, 11 Tuscany, 1 Marche, 87 Latium, 2 Molise, 83 Campania, 2 Apulia, 2 Basilicata, 5 Calabria, 3 Sicily, 28 Sardinia,  - 56 were asymptomatic cases detected in blood donors ,  - 339 were West Nile Fever cases (of which: 1 imported from Kenya , 1  from Egypt and 1 from Maldives),  - 3 asymptomatic cases ,  - 8 unspecified cases.  -- Among confirmed cases, 72 fatalities have been recorded: 7 in Piedmont, 9 Lombardy, 1 Veneto, 2 Emilia-Romagna, 1 Marche, 19 Latium, 29 Campania, 2 Calabria, 1 Sicily, 1 Sardinia.  - The Case-Fatality ...

#Chronology of #H3N2 #human #influenza virus surface glycoprotein #adaptation from 1968 to 2019 reveals a surge of adaptation between 1997 and 2002

  ABSTRACT Subtype H3N2 influenza A viruses (IAVs), which emerged in 1968 to cause a pandemic, have shown continual circulation and adaptation that has necessitated frequent updates of candidate vaccine viruses . Here, we sought to determine how genetic changes in the hemagglutinin (HA) and neuraminidase of 21 antigenically distinct H3N2 IAVs isolated from 1968 to 2019 correlate with mammalian fitness and adaptation. We found a surge of adaptation between 1997 and 2002 , resulting in the emergence of A/Fujian/411/2002 (H3N2) and poor vaccine efficacy , leading to an epidemic during the 2003–2004 season. This surge was characterized by a large reduction in binding to mammalian-type α2,6-linked sialic acids and increased infectivity and replication kinetics in humanized Madin-Darby canine kidney cells. HA glycosylation also increased most rapidly from 1968 to 2004 and then plateaued. Symptomatic infections were only evident in mice following inoculation with viruses isolated in the 1...

#Tissue #tropism and functional #adaptation of the #SARS-CoV-2 #spike protein in a #fatal case of #COVID19

  ABSTRACT Systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to extrapulmonary tissues has been observed following acute infections. Autopsy studies further indicate tissue-specific virus diversity, including in immune-privileged sites . Questions remain on the viral dynamics leading to the tissue tropism of SARS-CoV-2, including evolutionary trajectories and functional adaptations that could impact persistence and transmission . In this study, we characterized SARS-CoV-2 genomes from 27 distinct tissues collected from an autopsy case where the patient had a primary immune deficiency . We identified tissue-specific virus genotypes , in some instances coexisting within the same sites, with mutations primarily in the receptor-binding domain of the spike protein. Protein simulations and isolation of infectious virus indicate combinations of spike substitutions that would lead to increased protein stability and stronger binding of the virus to host cells. ...

Low levels of #influenza #H5N1 HA and NA #antibodies in the #human population are boosted by seasonal #H1N1 infection but not by H3N2 infection or influenza #vaccination

  ABSTRACT An increase in the number of human cases of influenza A/H5N1 infection in the USA has raised concerns about the pandemic potential of the virus. Pre-existing population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody titers were detected in a cohort of 73 individuals . Conversely, bovine A/H5N1 NA-binding and neuraminidase-inhibiting antibody titers were comparable to those against a human A/H1N1 NA at baseline . Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1-n...

#Genetic and #antigenic characteristics of #zoonotic #influenza A viruses and development of candidate #vaccine viruses for pandemic preparedness (#WHO, Oct. 31 '25)

  September 2025   The development of influenza candidate vaccine viruses (CVVs), coordinated by WHO, remains an essential component of the overall global strategy for influenza pandemic preparedness . Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture . National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production , clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.  Zoonotic influenza viruses continue to be identified and evolve both antigenically and genetically, leading to the need for additional CVVs for pandemic preparedness purposes.  Changes in the antigenic and genetic characteristics of these viruses relative to existing CVVs and their potential risks to public health justify the need to develop new CVVs. This document summarizes the antigenic and genetic c...

#Bulgaria - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification [FINAL]

  {By Subramanya CK - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17954283 } Two Western Marsh Harrier wild birds in Burgas Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6955 ____

#Hungary - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

  A fattening duck holding in Jász-Nagykun-Szolnok Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6959 ____

#Slovenia - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

A wild Mute Swan in Savinjska Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6964 ____

#Finland - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

{By  https://www.flickr.com/photos/sbern/ - https://www.flickr.com/photos/sbern/13471929904/ , CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=36391956 } A wild bird belonging to the Common Goldeneye Species. Source: WOAH,  https://wahis.woah.org/#/in-review/6956 ____

#Mpox Multi-country external #situation #report no. 59 published 30 October 2025 (#WHO, summary)

  Highlights     • This Situation report will now be published monthly.  • All clades of the monkeypox virus (MPXV) continue to circulate. When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, there is a risk of sustained community transmission.   • In September 2025, 42 countries , across all WHO regions, reported a total of 3135 confirmed cases , including 12 deaths (case fatality ratio [CFR] 0.4%). More than 80% of these cases were reported in the African Region . Four regions (African Region, Eastern Mediterranean Region, Region of the Americas, and the Western Pacific) observed a declining trend in confirmed cases reported per month, while the European and South-East Asian regions observed an increase in cases in September 2025. • Seventeen countries in Africa have experienced ongoing active transmission of mpox in the last six weeks (14 Sep – 19 Oct 2025), with 2862 confirmed cases, including 17 deaths (CFR ...