stilbenes and Influenza--Human

Given the magnitude of influenza pandemics as a threat to the global population, it is crucial to have as many prevention and treatment options as possible. Piceatannol (PIC) is a tetrahydroxylated stilbenoid (trans-3,4,3',5'-tetrahydroxystilbene), also known as 3'- hydroxy resveratrol, which has demonstrated many different biological activities such as anti-inflammatory and antiviral activities.. In this study, the anti-influenza A virus (IAV) activities and mechanisms of PIC in vitro and in vivo were investigated in order to provide reference for the development of novel plant-derived anti-IAV drugs.. The viral plaque assay, RT-PCR and western blot assay were used to evaluate the anti-IAV effects of PIC in vitro. The anti-IAV mechanism of PIC was determined by HA syncytium assay, DARTS assay and Surface Plasmon Resonance assay. The mouse pneumonia model combined with HE staining were used to study the anti-IAV effects of PIC in vivo.. PIC shows inhibition on the multiplication of both H1N1 and H3N2 viruses, and blocks the infection of H5N1 pseudovirus with low toxicity. PIC may directly act on the envelope of IAV to induce the rupture and inactivation of IAV particles. PIC can also block membrane fusion via binding to HA2 rather than HA1 and cleavage site of HA0. PIC may interact with the two residues (HA2-T68 and HA2-I75) of HA2 to block the conformational change of HA so as to inhibit membrane fusion. Importantly, oral therapy of PIC also markedly improved survival and reduced viral titers in IAV-infected mice.. PIC possesses significant anti-IAV effects both in vitro and in vivo and may block IAV infection mainly through interaction with HA to block membrane fusion. Thus, PIC has the potential to be developed into a new broad-spectrum anti-influenza drug for the prevention and treatment of influenza.

Topics: Animals; Disease Models, Animal; Hemagglutinins; Humans; Influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; Influenza, Human; Mice; Stilbenes

The anti-influenza virus activities of 50 resveratrol (RV: 3, 5, 4'-trihydroxy-trans-stilbene) derivatives were evaluated using a neuraminidase (NA) activity assay. The results showed that 35 compounds exerted an inhibitory effect on the NA activity of the influenza virus strain A/PR/8/34 (H1N1) with 50% inhibitory concentration (IC50) values ranging from 3.56 to 186.1 μm. Next, the 35 RV derivatives were used to develop 3D quantitative structure-activity relationship (3D QSAR) models for understanding the chemical-biological interactions governing their activities against NA. The comparative molecular field analysis (CoMFA r2=0.973, q2=0.620, qtest2=0.661) and the comparative molecular similarity indices analysis (CoMSIA r2=0.956, q2=0.610, qtest2=0.531) were applied. Afterward, molecular docking was performed to study the molecular interactions between the RV derivatives and NA. Finally, a cytopathic effect (CPE) reduction assay was used to evaluate the antiviral effects of the RV derivatives in vitro. Time-of-addition studies demonstrated that the RV derivatives might have a direct effect on viral particle infectivity. Our results indicate that the RV derivatives are potentially useful antiviral compounds for new drug design and development for influenza treatment.

Topics: Animals; Antiviral Agents; Cell Line; Dogs; Drug Design; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Molecular Docking Simulation; Neuraminidase; Orthomyxoviridae Infections; Quantitative Structure-Activity Relationship; Resveratrol; Stilbenes

Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits.

Topics: Animals; Antiviral Agents; Cell Line; DNA-Directed RNA Polymerases; Dogs; Humans; Influenza A virus; Influenza, Human; Orthomyxoviridae Infections; Phthalimides; Stilbenes; Thalidomide

Poison center data are increasingly used by state health departments and the Centers for Disease Control and Prevention for public health surveillance. Forrester and colleagues evaluated the ability of 6 Texas poison centers covering a population of 24 million to accurately code and report the number of H1N1 calls received over a 5-month period.. The Texas poison centers generated new coding and began work within 24 h of notification of the surveillance need. No additional staff were added for call management, coding, or quality assurance, and no H1N1 training was provided ahead of time. A triple-redundancy coding method was used to prevent underreporting of calls. This allowed the Texas poison centers to accurately flag over 90% of H1N1 cases. Results were available in real time, allowing day-to-day monitoring by poison centers and the state public health department for surges, location, ages of callers and/or patients, and type of question.. The accuracy of poison center near real-time toxicosurveillance data coding was sufficient to monitor emerging trends. The data generated by poison centers are flexible, immediate, unique from other data sources, and useful for trend monitoring. As health departments and other collaborative partners rely more on the data from poison centers, consideration must be given to appropriate funding to support coding training, monitoring, and quality assurance to further enhance this valuable system.

Topics: Data Collection; Forms and Records Control; Health Services Accessibility; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Population Surveillance; Research Design; Stilbenes; Texas