Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza A virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution

Publication date: Available online 6 April 2020Source: Antiviral ResearchAuthor(s): Saori Suzuki, Shintaro Shichinohe, Yasushi Itoh, Misako Nakayama, Hirohito Ishigaki, Yuya Mori, Ayako Ogata-Nakahara, Cong Thanh Nguyen, Masatoshi Okamatsu, Yoshihiro Sakoda, Hiroshi Kida, Kazumasa Ogasawara
Source: Antiviral Therapy - Category: Virology Source Type: research

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We report here on a series of benzo[d]thiazole and 4,5,6,7-tetrahydrobenzo[d]thiazole derivatives with robust and selective activities against influenza A (H1N1, H3N2) and influenza B viruses. Two compounds, 1 and 4, have low micromolar EC50 values and show high binding affinities for Hsp90, which suggests that inhibition of Hsp90 is the mechanism underlying their antiviral effects. These compounds represent suitable scaffolds for designing novel Hsp90 inhibitors with favourable activities against influenza virus. PMID: 32171985 [PubMed - as supplied by publisher]
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research
Abstract In the endemic settings of India, high CFR (3.6-7.02%) was observed in the consecutive 2009, 2015 and 2017 A/H1N1pdm09 outbreaks, though in eastern India CFR varied between 0 and 5.5% during same period. Recurrent outbreaks of pandemic Influenza A/H1N1pdm09, fragmented nationwide incidence data, lack of national policy for Influenza vaccination in India underscores the necessity for generating regional level data. Thus, during 2017-19, 4106 referred samples from patients hospitalized with severe acute respiratory illness (SARI) in eastern India were tested for A/H1N1pdm09 infection. Among which 16.5% (n...
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research
Publication date: Available online 27 February 2020Source: Antiviral ResearchAuthor(s): Hongyu Qiu, Hanne Andersen, E. Bart Tarbet, F. Salih Muhammad, Trevor Carnelley, Russell Pronyk, Douglas Barker, Shantha Kodihalli
Source: Antiviral Therapy - Category: Virology Source Type: research
In this study, we show that OA-10, a newly synthesized triterpene out of 11 oleanane-type derivatives, exhibited significant antiviral activity against four different subtypes of IAV (H1N1, H5N1, H9N2 and H3N2) replications in A549 cell cultures with EC50 ranging from 6.7 to 19.6 μM and a negligible cytotoxicity (CC50 > 640 μM). It inhibited acid-induced hemolysis in a dose-dependent manner, with an IC50 of 26 µM, and had a weak inhibition on the adsorption of H5 HA to chicken erythrocytes at higher concentrations (≥40 µM). Surface plasmon resonance (SPR) analysis showed that...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
Purpose of review Overview of influenza infection, focusing on outcome and complications in critically ill patients. We also discuss relevant elements in immunopathogenesis and their role as predictors of severity. Recent findings Pandemic influenza A (H1N1) virus circulates seasonally and remains the predominant subtype among intensive care patients. Mortality in acute respiratory failure (ARF) is around 20%, independent of influenza subtypes. During severe infection, the imbalance between pro-inflammatory and anti-inflammatory molecules, such as Th1 and Th17 cytokines, is associated with complicated infections and m...
Source: Current Opinion in Critical Care - Category: Nursing Tags: SEVERE INFECTIONS: Edited by Michael S. Niederman Source Type: research
We examined the prophylactic and therapeutic efficacy of CAM against H5N1 highly pathogenic and H7N9 low pathogenic avian influenza virus infections in cynomolgus monkeys. CAM suppressed H5N1 virus-induced severe signs of disease in the treated monkeys and inhibited virus propagation in tracheal samples and the production of inflammatory cytokines in the lungs of monkeys infected with H5N1 and H7N9 viruses. The prophylactic administration of CAM showed more suppressive effects on clinical signs of disease and viral titers than did therapeutic administration. Thus, since administration of CAM alone showed a tendency to amel...
Source: Antiviral Therapy - Category: Virology Source Type: research
Publication date: Available online 9 July 2019Source: Antiviral ResearchAuthor(s): Mingxin Li, Li Chen, Qingguang Wang, Mengchan Hao, Xiaoqing zhang, Linlin Liu, Xiao Yu, Chunpeng Yang, Junqiang Xu, Jianjun Chen, Rui GongAbstractSubtype H7 avian influenza viruses have been found to be associated with human infection and represent a risk for global public health. In 2013, the emergence of H7N9 virus in human beings and persistent human infection in China raised the most serious pandemic threat. Here we identified a human monoclonal antibody, P52E03, targeting the hemagglutinin (HA) of subtype H7 influenza viruses (H7 antige...
Source: Antiviral Therapy - Category: Virology Source Type: research
Publication date: Available online 19 June 2019Source: Antiviral ResearchAuthor(s): Simone E. Adams, Nicolette Lee, Vladimir Y. Lugovtsev, Anastasia Kan, Raymond P. Donnelly, Natalia A. IlyushinaAbstractNeuraminidase inhibitors (NAIs) play a key role in the management of influenza. Given the limited number of FDA-approved anti-influenza drugs, evaluation of potential drug-resistant variants is of high priority. Two NA mutations, V116A and I117V, are found in ∼0.6% of human, avian, and swine N1 isolates. Using the A/California/04/09-like (CA/04, H1N1) background, we examined the impact of V116A and I117V NA mutations on...
Source: Antiviral Therapy - Category: Virology Source Type: research
Publication date: Available online 25 May 2019Source: Antiviral ResearchAuthor(s): R. Farrukee, J. Butler, P.C. Reading, A.C. HurtAbstract:Avian A(H7N9) infections in humans have been reported in China since 2013 and are of public health concern due to their severity and pandemic potential. Oseltamivir and peramivir are neuraminidase inhibitors (NAIs) routinely used for the treatment of A(H7N9) infections, but variants with reduced sensitivity to these drugs can emerge in patients during treatment. Zanamivir and laninamivir are NAIs that are used less frequently. Herein, we performed in vitro serial passaging experiments w...
Source: Antiviral Therapy - Category: Virology Source Type: research
We describe the unexpected binding of S-layer to cells devoid of DC-SIGN but also confirm that the presence of DC-SIGN was essential for S-layer’s antiviral activity. S-layer protein exerted its antiviral effect with different kinetics than mannan, a known viral inhibitor that also acts on DC-SIGN (Yu et al., 2017). Together our results suggest that inhibition of viral entry by S-layer occurs via a novel S-layer/DC-SIGN interaction. Materials and Methods Isolation of S-Layer Proteins S-layer proteins were extracted from overnight cultures of L. acidophilus ATCC 4356 cells grown in MRS medium at 37°C by using 6...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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