From high-throughput to therapeutic: host-directed interventions against influenza viruses

2022 ◽  
Vol 53 ◽  
pp. 101198
Author(s):  
Joseph D Trimarco ◽  
Nicholas S Heaton
2013 ◽  
Vol 9 ◽  
pp. 197-203 ◽  
Author(s):  
Terry W Moore ◽  
Kasinath Sana ◽  
Dan Yan ◽  
Pahk Thepchatri ◽  
John M Ndungu ◽  
...  

High-throughput screening (HTS) previously identified benzimidazole 1 (JMN3-003) as a compound with broad antiviral activity against different influenza viruses and paramyxovirus strains. In pursuit of a lead compound from this series for development, we sought to increase both the potency and the aqueous solubility of 1. Lead optimization has achieved compounds with potent antiviral activity against a panel of myxovirus family members (EC50 values in the low nanomolar range) and much improved aqueous solubilities relative to that of 1. Additionally, we have devised a robust synthetic strategy for preparing 1 and congeners in an enantio-enriched fashion, which has allowed us to demonstrate that the (S)-enantiomers are generally 7- to 110-fold more potent than the corresponding (R)-isomers.


Author(s):  
Nicole B. Goecke ◽  
Jesper S. Krog ◽  
Charlotte K. Hjulsager ◽  
Kerstin Skovgaard ◽  
Timm C. Harder ◽  
...  

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Emilie Bonin ◽  
Stéphane Quéguiner ◽  
Cédric Woudstra ◽  
Stéphane Gorin ◽  
Nicolas Barbier ◽  
...  

2011 ◽  
Vol 16 (7) ◽  
Author(s):  
I Huber ◽  
H Campe ◽  
D Sebah ◽  
C Hartberger ◽  
R Konrad ◽  
...  

For surveillance purposes real-time PCR assays for influenza viruses had to be adapted to the pandemic influenza A(H1N1)2009 strain. We combined published primers and probes for influenza A, influenza B and an internal amplification control with a detection system for influenza A(H1N1)2009 to set up a rapid, reliable, simple and cost-effective high-throughput multiplex one-step real-time RT-PCR. The workflow also includes automated sample preparation for high-throughput screening. The lower limit of detection of the multiplex assay was 3.5x102 RNA copies per PCR reaction. The diagnostic sensitivity of the multiplex assay was 87.7%, but increased to 99.4% for influenza-positive samples yielding Ct values of less than 34 cycles in the respective diagnostic assay. High specificity was confirmed by sequencing and correct detection of 15 reference samples from two quality assurance studies. The multiplex PCR was introduced for surveillance of samples from a network of general practitioners and paediatricians in Bavaria, Germany during the influenza pandemic of 2009. Comparison with surveillance data from reported cases proved the reliability of the multiplex assay for influenza surveillance programmes.


2011 ◽  
Vol 3 (3) ◽  
pp. 283-296 ◽  
Author(s):  
Weng-I Lao ◽  
Ya-Fang Wang ◽  
Yu-Dai Kuo ◽  
Chun-Hung Lin ◽  
Tsung-Chain Chang ◽  
...  

2013 ◽  
Vol 13 (1) ◽  
pp. 34 ◽  
Author(s):  
Sven N Hobbie ◽  
Karthik Viswanathan ◽  
Ido Bachelet ◽  
Udayanath Aich ◽  
Zachary Shriver ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Temitope O. C. Faleye ◽  
Deborah Adams ◽  
Sangeet Adhikari ◽  
Helen Sandrolini ◽  
Rolf U. Halden ◽  
...  

Abstract Background Local transmission of seasonal influenza viruses (IVs) can be difficult to resolve. Here, we study if coupling high-throughput sequencing (HTS) of hemagglutinin (HA) and neuraminidase (NA) genes with variant analysis can resolve strains from local transmission that have identical consensus genome. We analyzed 24 samples collected over four days in January 2020 at a large university in the US. We amplified complete hemagglutinin (HA) and neuraminidase (NA) genomic segments followed by Illumina sequencing. We identified consensus complete HA and NA segments using BLASTn and performed variant analysis on strains whose HA and NA segments were 100% similar. Results Twelve of the 24 samples were PCR positive, and we detected complete HA and/or NA segments by de novo assembly in 83.33% (10/12) of them. Similarity and phylogenetic analysis showed that 70% (7/10) of the strains were distinct while the remaining 30% had identical consensus sequences. These three samples also had IAV and IBV co-infection. However, subsequent variant analysis showed that they had distinct variant profiles. While the IAV HA of one sample had no variant, another had a T663C mutation and another had both C1379T and C1589A. Conclusion In this study, we showed that HTS coupled with variant analysis of only HA and NA genes can help resolve variants that are closely related. We also provide evidence that during a short time period in the 2019–2020 season, co-infection of IAV and IBV occurred on the university campus and both 2020/2021 and 2021/2022 WHO recommended H1N1 vaccine strains were co-circulating.


Author(s):  
Dominik Nörz ◽  
Armin Hoffmann ◽  
Martin Aepfelbacher ◽  
Susanne Pfefferle ◽  
Marc Lütgehetmann

Introduction. Laboratories worldwide are facing high demand for molecular testing during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which might be further aggravated by the upcoming influenza season in the northern hemisphere. Gap Statement. Given that the symptoms of influenza are largely indistinguishable from those of coronavirus disease 2019 (COVID-19), both SARS-CoV-2 and the influenza viruses require concurrent testing by RT-PCR in patients presenting with symptoms of respiratory tract infection. Aim. We adapted and evaluated a laboratory-developed multiplex RT-PCR assay for simultaneous detection of SARS-CoV-2 (dual target), influenza A and influenza B (SC2/InflA/InflB-UCT) on a fully automated high-throughput system (cobas6800). Methodology. Analytical performance was assessed by serial dilution of quantified reference material and cell culture stocks in transport medium, including pretreatment for chemical inactivation. For clinical evaluation, residual portions of 164 predetermined patient samples containing SARS-CoV-2 (n=52), influenza A (n=43) or influenza B (n=19), as well as a set of negative samples, were subjected to the novel multiplex assay. Results. The assay demonstrated comparable analytical performance to currently available commercial tests, with limits of detection of 94.9 cp ml−1 for SARS-CoV-2, 14.6 cp ml−1 for influenza A and 422.3 cp ml−1 for influenza B. Clinical evaluation showed excellent agreement with the comparator assays (sensitivity of 98.1, 97.7 and 100 % for Sars-CoV-2 and influenza A and B, respectively). Conclusion. The SC2/InflA/InflB-UCT allows for efficient high-throughput testing for all three pathogens and thus provides streamlined diagnostics while conserving resources during the influenza season.


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