Viruses, Vol. 12, Pages 225: An Oleanolic Acid Derivative Inhibits Hemagglutinin-Mediated Entry of Influenza A Virus

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 OA-10 interacted with HA in a dose-dependent manner with the equilibrium dissociation constants (KD) of the interaction of 2.98 × 10−12 M. Computer-aided molecular docking analysis suggested that OA-10 might bind to the cavity in HA stem region which is known to undergo significant rearrangement during membrane fusion. Our results demonstrate that OA-10 inhibits H5N1 IAV replication mainly by blocking the conformational changes of HA2 subunit required for virus fusion with endosomal membrane. These findings suggest that OA-10 could serve as a lead for further development of novel virus entry inhibitors to prevent and treat IAV infections.
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research

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Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)–biomimetic liposomes encapsulating 2',3'-cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine–induced humoral and CD8+ T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP–adjuvanted H1N1 vaccine, strong cross-p...
Source: ScienceNOW - Category: Science Authors: Tags: Immunology, Microbiology, Online Only r-articles Source Type: news
Abstract Avian influenza A viruses (AIVs) classify into 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes. Even though H1N1 and H3N2 subtypes usually circulate among humans leading to infection, occasionally, H5, H6, H7, H9, and H10 that circulate in poultry also infect humans, and especially H5N1 and H7N9. Efficient virus replication is a critical factor that influences infection. Codon usage of a virus must coevolve with its host for efficient viral replication, therefore, we conduct a comprehensive analysis of codon usage bias in human-isolated AIVs to test their adaptation to host expression system. The...
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research
Contributors : Ariel Rodriguez-Frandsen ; Laura Martin-Sancho ; Anshu P Gounder ; Sumit K ChandaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensInfluenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, and sporadic pandemics due to human adaptation of pathogenic strains. Efficient replication of IAV in different species is, in part, dictated by its ability to exploit the genetic environment of the host cell. To investigate IAV tropism in human cells, we evaluated the replication of IAV strains in a diverse subset of epithelial cell lines. HeLa cells ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Publication date: 16 May 2019Source: Cell, Volume 177, Issue 5Author(s): Sandhya Bangaru, Shanshan Lang, Michael Schotsaert, Hillary A. Vanderven, Xueyong Zhu, Nurgun Kose, Robin Bombardi, Jessica A. Finn, Stephen J. Kent, Pavlo Gilchuk, Iuliia Gilchuk, Hannah L. Turner, Adolfo García-Sastre, Sheng Li, Andrew B. Ward, Ian A. Wilson, James E. CroweSummaryHere, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 he...
Source: Cell - Category: Cytology Source Type: research
In conclusion, the reported results highlight the importance of AIV attachment to trachea in many avian species. Finally, the importance of chickens and mallards in AIVs dynamics was illustrated by the abundant AIV attachment observed. Introduction Influenza A viruses (IAVs) are pathogens of global concern in both human and veterinary medicine (Webster et al., 1992; Stöhr, 2002; Olsen et al., 2006; Wiethoelter et al., 2015). Wild birds are well-described hosts of avian influenza viruses (AIVs) and longitudinal surveillance studies have demonstrated a plethora of low pathogenic AIVs (LPAIVs) circulating in wild...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusions: Human challenge studies and systems biology approaches are important tools that should be used in concert to advance our understanding of influenza infection and provide targets for novel therapeutics and immunizations. Introduction Although influenza virus was recognized as an important pathogen over a century ago, influenza continues to cause a significant burden of disease. In the United States alone, it's estimated that in the 2017–2018 season there were 959,000 hospitalizations related to influenza illness, and 79,400 deaths (CDC, 2018). Worldwide, WHO estimates that annual influenza...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Jennifer M. Rudd1, Sivasami Pulavendran1, Harshini K. Ashar1, Jerry W. Ritchey1, Timothy A. Snider1, Jerry R. Malayer1, Montelongo Marie1, Vincent T. K. Chow2 and Teluguakula Narasaraju1* 1Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States2Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore Exaggerated host innate immune responses have been implicated in severe influenza pneumonia. We have previously demonstrated that excessive neutrophils recruited during in...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
The objective of this preclinical study was to assess the protective immunity induced by immunization with group 1 hemagglutinin-specific influenza virus vaccines based on chimeric hemagglutinins (cHAs) in a ferret model of influenza. The experimental designs and immunization strategies are summarized in Figure 1. Since most human adults have a primed repertoire of B cells with specificity to the HA stalk domain (19, 30), we included an influenza B virus expressing cH9/1 (B-cH9/1) to mimic pre-existing HA stalk immunity. We then compared the ability of our sequential immunization strategies to boost antibody titers against...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Contributors : Matthew Urbanowski ; Megan Shaw ; Alex Rialdi ; Ivan Marazzi ; Sven Heinz ; Chris Benner ; Max Chang ; Lars Pache ; Randy Albrecht ; Adolfo Garcia-SastreSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensHuman tracheobronchial epithelial (HTBE) cells are considered to serve as a good correlate of influenza virus infection in the human respiratory tract. ChIP-Seq analysis was used to profile histone acetylation (H3K27ac) in HTBE cells at multiple time points in response to infection with influenza A/California/04/09 (H1N1), A/Wyoming/03/03 (H3N2), and A/Vietna...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
CONCLUSION: Our study reveals the emergence and spread of antiviral drug resistant influenza A viruses in the EMR and emphasizes the importance of continuous surveillance to maintain the effective use of the current antivirals. PMID: 30389548 [PubMed - as supplied by publisher]
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research
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