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Baptism of St Zenobius and His Appointment as Bishop (Sandro Botticelli, 1500 - 05)

 Public Domain. Source: WikiArt,  https://www.wikiart.org/en/sandro-botticelli/baptism-of-st-zenobius-and-his-appointment-as-bishop-1505 ____

#Evolution of #Antiviral Drug #Resistance in #SARS-CoV-2

Abstract The COVID-19 pandemic has had a significant impact and continues to alarm the entire world due to the rapid emergence of new variants , even after mass vaccinations . There is still an urgent need for new antivirals or strategies to combat the SARS-CoV-2 infections; however, we have success stories with nirmatrelvir . Drug repurposing and drug discovery may lead to a successful SARS-CoV-2 antiviral; however, rapid drug use may cause unexpected mutations and antiviral drug resistance. Conversely, novel variants of the SARS-CoV-2 can diminish the neutralizing efficacy of vaccines, thereby enhancing viral fitness and increasing the likelihood of drug resistance emergence. Additionally, the disposal of antivirals in wastewater also contributes to drug resistance. Overall, the present review summarizes the strategies and mechanisms involved in the development of drug resistance in SARS-CoV-2. Understanding the mechanism of antiviral resistance is crucial to mitigate the significant...

#WHO #clinical practice #guidelines for #influenza: an #update

Abstract Background Every year, more than one billion people around the world are infected with influenza , an acute infection of the respiratory tract. Influenza spreads from person to person through air, contaminated hands or objects. Antiviral and immunomodulatory drugs are available for treatment of patients and prophylaxis of exposed persons. Reverse transcription polymerase chain reaction (RT-PCR), nucleic acid amplification tests (NAATs) and rapid tests are available for the diagnosis of influenza.  Objective   The aim of this World Health Organization (WHO) guideline is to provide recommendations for the diagnosis, drug treatment and prophylaxis of influenza. Method This updated guideline has been developed in accordance with standards for trustworthy guidelines. The recommendations are based on systematic reviews on safety and effectiveness. They take into account the magnitude of benefits and harms of treatments, the reliability of the evidence, and the needs of pati...

#Coronavirus Disease Research #References (by AMEDEO, May 17 '25)

  Am J Respir Crit Care Med EDDY RL, Sin DD Loss of Lung Function Led to Loss of Life During the COVID-19 Pandemic. Am J Respir Crit Care Med. 2025. PubMed          Ann Intern Med JACOBS JW, Booth GS, Lewis-Newby M, Saifee NH, et al Medical, Societal, and Ethical Considerations for Directed Blood Donation in 2025. Ann Intern Med. 2025 May 13. doi: 10.7326/ANNALS-25-00815. PubMed           Abstract available BMJ WISE J Covid-19: Attitudes shifted after politicians broke rules, report says. BMJ. 2025;389:r960. PubMed          Br J Anaesth COPLEY S, Carty S, Brown M, Mishra S, et al Bridging the GAP: a critical analysis of pain management services in the United Kingdom. Br J Anaesth. 2025;134:1597-1602. PubMed           Abstract available Clin Infect Dis HAWKINS KL, Dandachi D, Verzani Z, Brannock MD, et al HIV Infection and Long COVID: ...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, May 17 '25)

  Biochem Biophys Res Commun PERFILOVA KV, Matyuta IO, Minyaev ME, Boyko KM, et al High-resolution structure reveals enhanced 14-3-3 binding by a mutant SARS-CoV-2 nucleoprotein variant with improved replicative fitness. Biochem Biophys Res Commun. 2025;767:151915. PubMed           Abstract available J Gen Virol AHMED MN, Abu Habib US, Abdallah AM, Emara MM, et al The impact of pre-existing immunity on the emergence of within-host immune-escape mutations in Omicron lineages. J Gen Virol. 2025;106:002108. PubMed           Abstract available J Immunol NOURI HR, Schaunaman N, Kraft M, Numata M, et al Tollip deficiency enhances mitophagy and reduces STING activation in influenza A virus-infected mice. J Immunol. 2025 May 16:vkaf058. doi: 10.1093. PubMed           Abstract available J Infect Dis ZHU S, Quint J, Leon T, Sun M, et al Estimating Influenza Vaccine Effectiv...

History of Mass Transportation: The FS E.444.001 Italian Electric Locomotive

  Source: Wikipedia,  https://it.wikipedia.org/wiki/Locomotiva_FS_E.444 By Manfred Kopka - Opera propria, CC BY-SA 4.0 ____

Assessment of cross-reactive neutralizing #antibodies induction against #H5N1 clade 2.3.4.4b by prior seasonal influenza #immunization in retail #workers

Abstract Highly pathogenic avian influenza (HPAI) H5N1 has been a global concern since its emergence in 1997, causing widespread outbreaks in birds and sporadic human infections . The clade 2.3.4.4b H5N1 virus has rapidly expanded across continents, infecting numerous mammalian species . In 2024, it was detected in dairy cattle for the first time in the U.S., along with human cases following exposure . In Canada , the first human case of this avian influenza was reported in a critically ill adolescent in late 2024. No human-to-human transmission has been documented, but concerns persist regarding mutations associated with enhanced virulence and human adaptation . Although seasonal influenza vaccines are not directed against H5N1, studies suggest that pre-existing immunity from prior infections or vaccinations may provide partial protection against severe H5N1 infections through cross-reactive immune response . Given the ongoing circulation of avian influenza and the rise in human infec...

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

  The Official Veterinary Services (OVS) received a notification of acute mortality, neurological and digestive signs in a breeder farm . From the start of the OVS investigation, the premise was quarantined, including suspension of the movement of birds and products. Laboratory analysis identified H5N1 virus clade 2.3.4.4b. OVS is conducting an epidemiological investigation of the event and implementing the restrictions and measures in accordance with the National Contingency Plan for high pathogenicity avian influenza (HPAI). Source: WOAH,  https://wahis.woah.org/#/in-review/6484 ____

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

Sudden death of birds, clinical signs, non-commercial hobby flock of hens, products are used exclusively for own consumption in the same household. Source: WOAH,  https://wahis.woah.org/#/in-review/6471 ____

Novel #Orthohantavirus Associated with #Hantavirus Pulmonary Syndrome in Northern #Argentina

Abstract In this work, we performed the genetic characterization of a new variant of orthohantavirus associated with a fatal case of hantavirus pulmonary syndrome , outside the known endemic region, in northwestern Argentina . We first confirmed an orthohantavirus infection by ELISA , testing for the detection of IgM and IgG antibodies. Then, we extracted RNA from 100 microliters of serum, the only sample available, followed by RT-PCR. The amplicons were sequenced using Sanger and next-generation sequencing technology. We obtained partial sequences of 1253 bp, 799 bp and 1675 bp from the S-, M- and L-segments, respectively, showing low sequence identities with all the previously characterized hantaviruses (10.9%, 13.5% and 15.1% of the divergence, respectively). The phylogenetic analysis showed that this virus belongs to the Orthohantavirus andesense species (ANDV), and among the ANDV-like variants, it is more closely related to the Lechiguanas clade . Similar percentages of divergence...

Yellow fever - Region of the #Americas (#WHO D.O.N., May 16 '25)

{Summary} Situation at a glance From 29 December 2024 and as of 26 April 2025 (with data for Ecuador updated as of 2 May 2025), a total of 212 confirmed human cases of yellow fever , including 85 deaths , have been reported to WHO by five countries in the Region of the Americas ( case fatality rate (CFR) 40% ).  The cases have been reported in the Plurinational State of Bolivia, Brazil, Colombia, Ecuador and Peru .  The 212 confirmed yellow fever cases reported so far in 2025 represent a threefold increase compared to the 61 confirmed cases reported in 2024.  WHO is supporting affected countries in implementing coordinated actions to respond to the yellow fever cases and outbreaks.  This includes:  - enhancing preventive measures,  - strengthening surveillance and case management,  - improving risk communication and community engagement, and  - implementing immunization activities.  The current yellow fever situation in the Americas is driven...

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (CDC, May 16 '25)

  {Excerpt} Time Period: April 27, 2025 - May 03, 2025 -- H5 Detection :  8 sites ( 2.0% ) - No Detection :  402 sites ( 98.0% ) - No samples in last week :  67 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html ____

#Molnupiravir or #nirmatrelvir–ritonavir plus usual care vs usual care alone in patients admitted to #hospital with #COVID19 (RECOVERY)...

Summary Background Molnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce. Methods The RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19 . In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia ; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants coul...

Identification of naturally occurring #drug-resistant #mutations of #SARS-CoV-2 papain-like #protease

Abstract The SARS-CoV-2 papain-like protease (PLpro) is a cysteine protease that cleaves viral polyproteins and antagonizes the host immune response during viral replication. Jun12682 and PF-07957472 are the first-in-class PLpro inhibitors showing potent in vivo antiviral efficacy in mouse models . In this study, we characterize naturally occurring mutations at residues located at the drug-binding site of Jun12682. The results reveal several PLpro mutants showing significant drug resistance while maintaining comparable enzymatic activity as the wild-type PLpro. The physiological relevance of the identified drug-resistant mutants, including E167G and Q269H, is validated through independent serial viral passage experiments. Molecular dynamics simulations and perturbative free energy calculations show that drug-resistant PLpro mutants weaken hydrogen bonding and π-π stacking interactions. Collectively, this study identifies E167, Y268, and Q269 as drug-resistant hotspots for PLpro inhibit...

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...