Characterization of substitutions in the neuraminidase of A(H7N9) influenza viruses selected following serial passage in the presence of different neuraminidase inhibitors

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 with recombinant viruses, containing the neuraminidase (NA) from influenza A/Anhui/1/13 (H7N9) virus, in the presence of each NAI, to determine whether variants with reduced sensitivity would emerge. NA substitutions were characterized for their effect on the NA enzymatic activity and surface expression of the A/Anhui/1/13 (Anhui/1) NA, as well as NAs originating from contemporary A(H7N9) viruses of the Yangtze River Delta and Pearl River Delta lineages. In vitro passage in the presence of oseltamivir, peramivir and laninamivir selected for substitutions associated with reduced sensitivity (E119D, R292K and R152K), whereas passage in the presence of zanamivir did not select for any viruses with reduced sensitivity. All the NA substitutions significantly reduced activity, but not the expression of the Anhui/1 NA. In contemporary N9 NAs, all substitutions teste...
Source: Antiviral Therapy - Category: Virology Source Type: research

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Publication date: Available online 8 April 2019Source: Antiviral ResearchAuthor(s): John H. Beigel, Hannah H. Nam, Peter L. Adams, Amy Krafft, William L. Ince, Samer S. El-Kamary, Amy C. SimsAbstractThe International Society for Influenza and other Respiratory Virus Diseases held its 6th Antiviral Group (isirv-AVG) conference in Rockville, Maryland, November 13–15, 2018. The three-day program was focused on therapeutics towards seasonal and pandemic influenza, respiratory syncytial virus, coronaviruses including MERS-CoV and SARS-CoV, human rhinovirus, and other respiratory viruses. Updates were presented on several ...
Source: Antiviral Therapy - Category: Virology Source Type: research
In this study, we reported to obtain highly immunogenic influenza VLPs by molecular incorporation with B-cell-activating factor (BAFF) or proliferation-inducing ligand (APRIL). Since BAFF and APRIL act as homotrimers to interact with their receptors, we engineered the VLPs by direct fusion of BAFF or APRIL to the transmembrane anchored domain of H5HA gene. Results showed that immunizations with the HA-transmembrane anchored BAFF- or APRIL-VLPs only formulated in alum but not MPL adjuvant elicited significantly higher IgG titers in sera. However, only the BAFF-VLPs formulated in alum adjuvant elicited more broadly neutraliz...
Source: Antiviral Therapy - Category: Virology Source Type: research
Authors: Abstract Pregnant and postpartum women are at high risk of serious complications of seasonal and pandemic influenza infection. Pregnancy itself is a high-risk condition, making the potential adverse effects of influenza particularly serious in pregnant women. If a pregnant woman has other underlying health conditions, the risk of adverse effects from influenza is even greater. Antiviral treatment is necessary for all pregnant women with suspected or confirmed influenza, regardless of vaccination status. Obstetrician-gynecologists and other obstetric care providers should promptly recognize the symptoms o...
Source: Obstetrics and Gynecology - Category: OBGYN Tags: Obstet Gynecol Source Type: research
Authors: Abstract Pregnant and postpartum women are at high risk of serious complications of seasonal and pandemic influenza infection. Pregnancy itself is a high-risk condition, making the potential adverse effects of influenza particularly serious in pregnant women. If a pregnant woman has other underlying health conditions, the risk of adverse effects from influenza is even greater. Antiviral treatment is necessary for all pregnant women with suspected or confirmed influenza, regardless of vaccination status. Obstetrician-gynecologists and other obstetric care providers should promptly recognize the symptoms o...
Source: Obstetrics and Gynecology - Category: OBGYN Tags: Obstet Gynecol Source Type: research
Publication date: Available online 17 August 2018Source: Antiviral ResearchAuthor(s): Richa Sood, Naveen Kumar, Sandeep Bhatia, Khangembam Victoria Chanu, Chhedi Lal Gupta, Atul Kumar Pateriya, Anamika Mishra, Rekha Khandia, Namrata Mawale, Vijendra Pal SinghAbstractWe tested 65 highly pathogenic avian influenza (HPAI) A(H5N1) viruses, isolated from avian species in India between 2006 and 2015, for susceptibility to the FDA approved neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir using a phenotypic fluorescence-based assay. The overall incidence of resistant variants among HPAI A(H5N1) viruses was 7.69% (5/...
Source: Antiviral Therapy - Category: Virology Source Type: research
Publication date: Available online 21 March 2018 Source:Antiviral Research Author(s): Jennifer L. McKimm-Breschkin, Susan Barrett, Frank Y.K. Wong, Pudjiatmoko, Muhammad Azhar, Paul Selleck, Kelly R. Davies, Nining Hartaningsih, James McGrane We have tested the in vitro susceptibility to the neuraminidase (NA) inhibitors of 96 highly pathogenic clade 2.1 A(H5N1) viruses from Indonesia, isolated between 2008 and 2011. HPAI virus samples obtained through the Influenza Virus Monitoring (IVM) surveillance program in Indonesia were tested for susceptibility to oseltamivir and zanamivir. The NAs of four viruses were identified ...
Source: Antiviral Therapy - Category: Virology Source Type: research
Publication date: Available online 7 March 2018 Source:Antiviral Research Author(s): Leen Delang, Rana Abdelnabi, Johan Neyts Favipiravir, also known as T-705, is an antiviral drug that has been approved in 2014 in Japan to treat pandemic influenza virus infections. The drug is converted intracellularly into its active, phosphoribosylated form, which is recognized as a substrate by the viral RNA-dependent RNA polymerase. Interestingly, besides its anti-influenza virus activity, this molecule is also able to inhibit the replication of flavi-, alpha-, filo-, bunya-, arena-, noro-, and of other RNA viruses, which include neg...
Source: Antiviral Therapy - Category: Virology Source Type: research
Abstract Favipiravir, also known as T-705, is an antiviral drug that has been approved in 2014 in Japan to treat pandemic influenza virus infections. The drug is converted intracellularly into its active, phosphoribosylated form, which is recognized as a substrate by the viral RNA-dependent RNA polymerase. Interestingly, besides its anti-influenza virus activity, this molecule is also able to inhibit the replication of flavi-, alpha-, filo-, bunya-, arena-, noro-, and of other RNA viruses, which include neglected and (re)emerging viruses for which no antiviral therapy is currently available. We will discuss the po...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
In this study, we used a novel PELC/CpG adjuvant for recombinant H7HA (rH7HA) subunit vaccine development. After immunizing BALB/c mice intramuscularly, rH7HA proteins formulated in this adjuvant instead of an alum adjuvant elicited higher IgG, hemagglutination-inhibition, and virus neutralizing antibodies in sera; induced higher numbers of H7HA-specific IFN-γ-secreting T cells and antibody secreting cells in spleen; and provided improved protection against live virus challenges. Our results indicate that rH7HA proteins formulated in PELC/CpG adjuvant can induce potent anti-H7N9 immunity that may provide useful infor...
Source: Antiviral Therapy - Category: Virology Source Type: research
Authors: Çörtük M, Acat M, Yazici O, Yasar Z, Kiraz K, Ataman SY, Tanriverdi E, Zitouni B, Kirakli C, Ediboglu O, Tuksavul F, Dirican A, Celik HK, Ozkaya S, Cetinkaya E Abstract Influenza A (H1N1) caused its first pandemic in 2009 in USA and Mexico. Since then, clinicians have exercised great care in order to make an early diagnosis of viral pneumonias. This is due in part to pandemic influenza A infection having greater impact on populations
Source: Experimental and Therapeutic Medicine - Category: Journals (General) Tags: Exp Ther Med Source Type: research
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