Abstract
Influenza A virus is a negative RNA stranded virus of the family Orthomyxoviridae, and represents a major public health threat, compounding existing disease conditions. Influenza A virus replicates rapidly within its host and the segmented nature of its genome facilitates re-assortment, whereby whole genes are exchanged between influenza virus subtypes during replication. Antiviral medications are important pharmacological tools in influenza virus prophylaxis and therapy. However, the use of currently available antiviral is impeded by sometimes high levels of resistance in circulating virus strains. Here, we identified novel anti-influenza compounds through screening of chemical compounds synthesized de novo on human lung epithelial cells. Computational and experimental screening of extensive and water soluble compounds identified novel influenza virus inhibitors that can reduce influenza virus infection without detectable toxic effects on host cells. Interestingly, the indicated active compounds inhibit viral replication most likely via interaction with cell receptors and disturb influenza virus entry into host cells. Collectively, screening of new synthesis chemical compounds on influenza A virus replication provides a novel and efficacious anti-influenza compounds that can inhibit viral replication via disturbing virus entry and indicates that these compounds are attractive candidates for evaluation as potential anti-influenza drugs.
Highlights
Influenza A virus (IAV) belongs to the family Orthomyxoviridae, and is considered as one of the most dangerous viruses that threaten human entity and causing up to 500,000 deaths per year worldwide
The preliminary results indicated by luciferase screening showed strong reduction of virus particles in A549 cells that overnight incubated with compounds EMT-104, EMT-300, EMT-301, and EMT-305 compared to infected cells (IN) and noninfected cells (NI) (Figure 1B)
Dimethyl sulfoxide (DMSO) is an organic compound with a median lethal dose higher than ethanol usually used at concentration of 30 mM to dissolve hydrophobic compounds
Summary
Influenza A virus (IAV) belongs to the family Orthomyxoviridae, and is considered as one of the most dangerous viruses that threaten human entity and causing up to 500,000 deaths per year worldwide. Zanamavir (Relenza) and oseltamivir (Tamiflu) are effective against subtypes of both IAV and Influenza B virus These compounds inhibit the viral glycoprotein, neuraminidase, so that the release of new virus particles is inhibited and spreading infections are limited (Ward et al, 2005; Yen et al, 2007). Genome wide RNAi screens have revealed that many host cell factors are essential for the replication of IAV (Hao et al, 2008; Karlas et al, 2010; Konig et al, 2010) These factors are attractive candidates for potential antiviral medications as it is less likely that influenza viruses will develop resistance rapidly to drugs that target host cell factors. Screening of these compounds reveals some attractive candidates that successfully reduced viral replication without any detectable toxic effect most likely via disturbing viral entry
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
