naphthoquinones and Influenza--Human

Results of experimental study on the effect of bonafton, tebrofen, florenal and riodoxol on synthesis of virus specific proteins and RNA are presented. Selective inhibition of RNA-transcripts and respective proteins under the effect of bonafton was revealed. Florenal had a selective inhibitory effect on synthesis of virus specific proteins. Riodoxol did not inhibit synthesis of viral RNA and proteins of the influenza virus.

Topics: Antiviral Agents; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Drug Evaluation, Preclinical; Fluorenes; Humans; In Vitro Techniques; Influenza A virus; Influenza, Human; Naphthoquinones; Polybrominated Biphenyls; Resorcinols; RNA, Viral; Viral Proteins

This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism. MDCK and A549 cells were used to investigate influenza viral infection and the structure-activity relationship between PMM-034 and NA was evaluated by pharmacophore-based docking modeling. The production of viral protein was tested by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM-034 to 16μg/mL and this showed a selective index of 10mM. PMM-034 inhibited NA in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease in viral nucleocapsid protein mRNA was observed in infected cells after treatment with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding pocket of NA bound to PMM-034 in the docking model. Taken together, these results suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential anti-H1N1 drug.

Topics: A549 Cells; Animals; Antiviral Agents; Apoptosis; Cell Line; Cell Line, Tumor; Dogs; Enzyme Inhibitors; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Madin Darby Canine Kidney Cells; Naphthoquinones; Orthomyxoviridae Infections; Oseltamivir; Structure-Activity Relationship; Viral Proteins

Topics: Adamantane; Adolescent; Adult; Aged; Codeine; Critical Care; Dipyrone; Drug Evaluation; Ephedrine; gamma-Globulins; Gossypol; Humans; Imidazoles; Influenza, Human; Interferons; Lactoglobulins; Middle Aged; Naphthoquinones; Oxygen Inhalation Therapy; Sympathomimetics; Time Factors

Topics: Adenoviridae Infections; Amantadine; Animals; Antibodies, Viral; Communicable Disease Control; Complement Fixation Tests; Computers; Fluorescent Antibody Technique; Genetics, Microbial; Humans; Influenza Vaccines; Influenza, Human; Interferon Inducers; Interferons; Mucus; Mycoplasma Infections; Naphthoquinones; Nasal Mucosa; Orthomyxoviridae; Oxolinic Acid; Respiratory Syncytial Viruses; Respirovirus; USSR