ETIDIOH - NEW

Abstract It is essential to understand the molecular mechanisms of influenza antiviral therapeutics to evaluate their efficacy. Virus plaque assays are commonly used to assess the antiviral effects of drugs on virus replication ; however, this method is labor-intensive and can present challenges. We avoided this method by using a replication-competent influenza A virus (IAV) expressing a reporter fluorescent gene fused to the non-structural protein 1 (NS1) gene. The reporter IAV was detectable in normal human bronchoepithelial (NHBE) infected cells and offered an improved method to determine the therapeutic efficacy of the antiviral drugs probenecid and oseltamivir compared to a standard plaque assay. This method provides an excellent means for evaluating therapeutic approaches against IAV. Source: Viruses,  https://www.mdpi.com/1999-4915/17/3/335 ____

Abstract We report the detection of a clade 2.3.4.4b A(H5N1) reassortant virus with a neuraminidase surface protein derived from a North American lineage low-pathogenic avian influenza virus. This virus caused a widespread and ongoing outbreak across 45 poultry farms in British Columbia, Canada . Isolates from 8 farms reveal a mutation in the neuraminidase protein (H275Y) that is exceptionally rare among clade 2.3.4.4b viruses (present in 0.045% of publicly available clade 2.3.4.4b isolates). NA-H275Y is a well-known marker of resistance to the neuraminidase inhibitor oseltamivir . We demonstrate that this substitution maintains its resistance phenotype on the genetic background of H5N1 clade 2.3.4.4b viruses. Source: Emerging Microbes and Infections,  https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2469643 ____

Abstract To better manage seasonal and pandemic influenza infections , new drugs are needed with enhanced activity against amantadine- and rimantadine-resistant influenza A virus (IAV) strains containing the S31N variant of the viral M2 ion channel (M2S31N). Here we tested 36 amantadine analogs against a panel of viruses containing either M2S31N or the parental, M2 S31 wild-type variant (M2WT). We found that several analogs, primarily those with sizeable lipophilic adducts, inhibited up to three M2S31N-containing viruses with activities at least 5-fold lower than rimantadine, without inhibiting M2S31N proton currents or modulating endosomal pH. While M2WT viruses in passaging studies rapidly gained resistance to these analogs through the established M2 mutations V27A and/or A30T, resistance development was markedly slower for M2S31N viruses and did not associate with additional M2 mutations. Instead, a subset of analogs, exemplified by 2-propyl-2-adamantanamine (38), but not 2-(1-adama...

Abstract SARS-CoV-2 main protease, Mpro , is responsible for processing the viral polyproteins into individual proteins, including the protease itself. Mpro is a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g., E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g., P252L, T21I, L50F), which restore the fitness of viral replication. To probe the role of the non-active site mutations in fitness rescue, here we use an Mpro triple mutant (L50F/E166A/L167F) that confers nirmatrelvir drug resistance with a viral fitness level similar to the wild-type. By comparing peptide and full-length Mpro protein as substrates, we demonstrate that the binding of Mpro substrate involves more than residues in the active site. Particularly, L50F and other non-active site mutations...

Abstract Introduction :  Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections , due to the widespread use of indwelling medical devices , total parenteral nutrition , systemic corticosteroids , cytotoxic chemotherapy , and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality , and drug resistance issues on a global scale. Methodology :  We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia . During his stay in the ward, he received systemic corticosteroids for a total duration of 32 days. A broad-spectrum antibiotic (piperacillin-tazobactam) was also given due to copious amounts of tracheostomy secretions . Results :  The patient’s fever recurred following an afebrile interval of 11 days...

Abstract As new SARS-CoV-2 variants continue to emerge , it is important to evaluate the potency of antiviral drugs to support their continued use. Remdesivir (RDV; VEKLURY®) an approved antiviral treatment for COVID-19, and obeldesivir (ODV) are inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. Here we show these two compounds retain antiviral activity against the Omicron variants BA.2.86, BF.7, BQ.1, CH.1.1, EG.1.2, EG.5.1, EG.5.1.4, FL.22, HK.3, HV.1, JN.1, JN.1.7, JN.1.18, KP.2, KP.3, LB.1, XBB.1.5, XBB.1.5.72, XBB.1.16, XBB.2.3.2, XBC.1.6, and XBF when compared with reference strains. Genomic analysis identified 29 Nsp12 polymorphisms in these and previous Omicron variants. Phenotypic analysis of these polymorphisms confirmed no impact on the antiviral activity of RDV or ODV and suggests Omicron variants containing these Nsp12 polymorphisms remain susceptible to both compounds. These data support the continued use of RDV in the context of circulating SARS-CoV-2 vari...

{Excerpt} The zoonotic Orthopoxvirus monkeypox virus includes two main clades (ie, 1 and 2) relevant to human transmission .1 Two major outbreaks of monkeypox virus have occurred since 2022,1–3 and were declared public health emergencies of international concern by WHO in July, 2022, and August, 2024. The first outbreak was caused by a clade 2b strain that quickly spread worldwide, resulting in approximately 100 000 cases and 200 deaths.3 In the second outbreak, the novel clade 1b emerged .4 As of December, 2024, this upsurge has resulted in more than 55 000 reported or suspected cases and approximately 1000 deaths in DR Congo and neighbouring countries, including Burundi, Rwanda, Uganda , and Angola .4 A few imported clade 1b cases have also been reported in the UK, Sweden, Germany, Belgium, France, the USA, Canada , and Thailand .5 Prevention measures include patient isolation and care as well as vaccines. (...) Source: Lancet Infectious Diseases,  https://www.thelancet.com/journ...

 {Summary} Swine influenza virus (SIV) is a highly contagious pathogen that poses significant economic challenges to the swine industry and carries zoonotic potential , underscoring the need for vigilant surveillance. In this study, we performed a comprehensive genetic and molecular analysis of H3N2 SIV isolates obtained from 372 swine samples collected in Shandong Province, China . Phylogenetic analysis revealed two distinct genotypes . The surface genes of both genotypes clustered with the human-like H3N2 lineage , while the internal genes of one genotype clustered with the 2009 pandemic H1N1 (pdm/09) lineage . In the second genotype, the NS gene clustered with the classical swine (CS) H1N1 lineage , while the remaining internal genes clustered with pdm/09, suggesting stable integration of pdm/09 gene segments into H3N2 SIV. Homology analysis showed over 96% genetic similarity between the isolates and reference strains from China and Brazil , suggesting potential transmission thr...

Natalia A. Ilyushina {a b}, Nicolai V. Bovin {c}, Robert G. Webster {a d}, Elena A. Govorkova  {a b} a} Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA; b} The D.I. Ivanovsky Institute of Virology, Gamaleya 16, Moscow 123098, Russia; c} Shemyakin Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia; d} Department of Pathology, University of Tennessee, Memphis, TN 38105, USA Received 21 November 2005, Accepted 26 January 2006, Available online 21 February 2006. Abstract Rapid development of resistant influenza variants after amantadine treatment is one of the main drawbacks of M2 blockers . On the other hand, the emergence of variants with low susceptibility to the neuraminidase (NA) inhibitors is limited. In the present study we examined whether combination therapy with two classes of anti-influenza drugs can affect the emergence of resistant variants in vitro. We observed that viru...