Narrow Results

The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR (0.1 ~ 100 μg/ml) to the infected cells did not have any inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW cells, a murine macrophage (Mφ) cell line, exhibited an apparent inhibitory effect on MDCK cells without cytotoxicity. In accordance with the time-dependent inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor (TNF)-α was gradually accumulated in ZOR-CM by the induction of TNF-α mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of ZOR-CM was reduced significantly by the removal of TNF-α after the formation of an immune complex with anti-TNF-α monoclonal antibody. These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-α.

We investigated the inhibitory effect of the conditioned medium (CM) from P338D1 (D1) cells, a murine macrophage cell line, stimulated for 10 hours with a fixed dose (100 μg/ml) of the extracts from the fruit bodies of Grifola frondosa (ME) or its ultra filtration-based fractions (MFs), on the growth of influenza A/Aichi/2/68 virus in Madin-Darby canine kidney cells. Direct addition of ME and 3 kinds of MFs (MF1, MF2 and MF3) to the infected cells had no obvious inhibitory effect. However, virus yields were reduced in the presence of CMs. Notably, the inhibitory effect of the CM prepared by using MF2 (molecular weight of 30 Kd to 100 Kd) was the strongest (28% reduction compared to the control). RT-PCR and ELISA assays showed that the CMs could induce the expression of TNF-α mRNA in D1 cells leading to production of TNF-α, known as an antiviral cytokine. These findings suggest that ME and MFs (especially MF-2) might induce the production of certain factors, including TNF-α, which are responsible for the inhibition of viral growth in vitro.

To study the oxidative stress level of the influenza virus A FM1 subset-infected mouse in intranasal inhalation as a model, we employ an ascorbyl radical's ESR (electron spin resonance) spectrum as an oxidative stress biomarker. These infected mice were pretreated with Ribavirin, ascorbic acid, superoxide dismutase (SOD) or Kegan Liyan oral prescription (KGLY, proprietary Chinese medicine for influenza and common cold) in the stomach tube for 3 days, and then followed by the virus-infecting for 4 days. On the 4th day, samples were collected. It is recognized the strength of ascorbyl radical's ESR signal (A^-.) (a_{H4 = 0.177} Gauss, g = 2.00517) denotes oxidative stress level in vivo and in vitro. The magnitude of ESR spectrum (28.65 ± 10.71 AU) in mice infected with influenza virus was significantly higher than those of healthy control mice (19.10 ± 3.61 AU). Serum A^-. in mice treated with Ribavirin, ascorbic acid, SOD and KGLY declined to 19.70 ± 6.05, 18.50 ± 2.93 and 16.25 ± 3.59, 18.40 ± 2.14 AU respectively. It is close to A^-. signal height in healthy controls via down-regulation of the influenza virus-caused oxidative stress level getting decline in the lung index of pneumonia as compare to those of untreated healthy and the influenza virus infected mice pneumonia. It is well known that SOD can prevent the influenza virus pneumonia enhancing mouse survival rate; Ribavirin can treat viral diseases. Data from this study suggested that KGLY may indirectly relieve influenza virus-infected pneumonia via down- regulation of virus caused oxidative stress coupled with a redox reaction cascade as ribavirin, ascorbic acid and SOD.

COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-$\alpha$, IL-6, and IL-1$\beta$ in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-$\alpha$, MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK$\alpha$/$\beta$, and I$\kappa$B$\alpha$ and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-$\kappa$B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.

In this paper, we have proposed and analyzed a simple model of Influenza spread with an asymptotic transmission rate. Existence and uniqueness of solutions are established and shown to be uniformly bounded for all non-negative initial values. We have also found a sufficient condition which ensures the persistence of the model system. This implies that both susceptible and infected will always coexist at any location of the inhabited domain. This coexistence is independent of values of the diffusivity constants for two subpopulations. The global stability of the endemic equilibrium is established by constructing a Lyapunov function. By linearizing the system at the positive constant steady-state solution and analyzing the associated characteristic equation, conditions for Hopf and Turing bifurcations are obtained. We have also studied the criteria for diffusion-driven instability caused by local random movements of both susceptible and infective subpopulations. Turing patterns selected by the reaction–diffusion system under zero flux boundary conditions have been explored.

Numerical simulations show that contact rate, β which is related to the reproduction number , plays an important role in spatial pattern formation. It was found that diffusion has appreciable influence on spatial spread of epidemics. The wave of chaos appears to be a dominant mode of disease dispersal. This suggests a bidirectional spread for influenza epidemics. The epidemic propagates in the form of nonchaotic and chaotic waves as observed in H1N1 incidence data of positive tests in 2009 in the United States. We have conducted numerical simulations to confirm the analytic work and observed interesting behaviors. This suggests that influenza has a complex dynamics of spatial spread which evolves with time.

Reliable and Fast Diagnosis of Influenza Virus.

Agilent Technologies Introduces Industry's First HPLC-Chip/MS System for Proteomics Research.

World's Smallest and Longest-Lasting Rechargeable Neurostimulator Gets Australia's Nod.

Chip-On-Chip and Gene Expression Used to Study How Yamanaka Factors Trigger Pluripotency.

New Antiviral Drug Discovery to Combat Influenza Virus.

DuPont Crop Protection Sees Research Synergies in Syngene's 'One Box' Model.

Ono Enters into Drug Discovery Agreement with Xention.

Eisai and Teikoku To Develop and Market Transdermal Patch for Treatment of Alzheimer's Disease.

Global Collaboration on Novel Atrial Fibrillation Compound.

Boston Scientific's Taxus Liberte Drug-Eluting Stent Launched in Japan.

Symansis Wins NZ Emerging Company Award.

Illumina's Entry Puts Singapore on Map as a Global Gene Chip Player.

Neste Oil's Renewable Biofuel Plant in Singapore Ready in 2010.

Singapore and US Collaborate—Leveraging Forma's Tranformative Chemistry Platform.

Influenza is one of the most important emerging and reemerging infectious diseases, causing high morbidity and mortality in communities (epidemic) and worldwide (pandemic). Here, classification of human vs. non-human influenza, and subtyping of human influenza viral strains virus is done based on profile hidden Markov models (HMM). The classical ways of determining influenza viral subtypes depend mainly on antigenic assays, which is time-consuming and not fully accurate. The introduced technique is much cheaper and faster, yet usually can still yield high accuracy. Multiple sequence alignments were done for the 16 HA subtypes and 9 NA subtypes, followed by profile-HMMs models generation, calibration and evaluation using the HMMER suite for each group. Subtyping accuracy of all HA and NA models achieved 100%, while host classification achieved accuracies around 53% and 95.1% according to HA subtype.

The influenza A (H5N1) virus attracts a worldwide attention and calls for the urgent development of novel antiviral drugs. In this study, explicitly solvated flexible docking and molecular dynamics (MD) simulations were used to study the interactions between the H5N1 sub-type hemagglutinin (HA) and various catechin compounds, including EC ([–]-epicatechin), EGC ([–]-epigallocatechin), ECG ([–]-epicatechin gallate) and EGCG ([–]-epigallocatechin gallate). The four compounds have respective binding specificities and their interaction energies with HA decrease in the order of EGCG (-133.52) > ECG (-111.11) > EGC (-97.94) > EC (-83.39). Units in kcal mol^-1. Residues IleA267, LysA269, ArgB68 and GluB78 play important roles during all the binding processes. EGCG has the best bioactivity and shows potential as a lead compound. Besides, the importance was clarified for the functional groups it was revealed that the C5′ hydroxyl and trihydroxybenzoic acid groups are crucial for the catechin inhibitory activities, especially the latter. Combined with the structural and property analyses, this work also proposed the way to effectively modify the functional groups of EGCG. The experimental efforts are expected in order to actualize the catechin derivatives as novel anti-influenza agents in the near future.

Interactions between integral membrane proteins hemagglutinin (HA), neuraminidase (NA), M2 and membrane-associated matrix protein M1 of influenza A virus are thought to be crucial for assembly of functionally competent virions. We hypothesized that the amino acid residues located at the interface of two different proteins are under physical constraints and thus probably co-evolve. To predict co-evolving residue pairs, the EvFold (http://evfold.org) program searching the (nontransitive) Direct Information scores was applied for large samplings of amino acid sequences from Influenza Research Database (http://www.fludb.org/). Having focused on the HA, NA, and M2 cytoplasmic tails as well as C-terminal domain of M1 (being the less conserved among the protein domains) we captured six pairs of correlated positions. Among them, there were one, two, and three position pairs for HA–M2, HA–M1, and M2–M1 protein pairs, respectively. As expected, no co-varying positions were found for NA–HA, NA–M1, and NA–M2 pairs obviously due to high conservation of the NA cytoplasmic tail. The sum of frequencies calculated for two major amino acid patterns observed in pairs of correlated positions was up to 0.99 meaning their high to extreme evolutionary sustainability. Based on the predictions a hypothetical model of pair-wise protein interactions within the viral envelope was proposed.

Ixeris chinensis (Thunb.) Nakai (I. chinensis), a commonly used Taiwanese herbal medicine that exhibits various pharmacological properties, has been used to prepare a traditional Chinese medicine composition for prevention and treatment of influenza A virus infection. In this study, the in vitro anti-influenza virus activity of I. chinensis was evaluated. The result showed that the 50% ethanol extract from I. chinensis significantly increased the viability of the DF-1 cells that were infected with the H6N1 influenza virus. This extract also suppressed the synthesis of viral nucleoprotein (NP) and inhibited the growth of the H6N1 virus in DF-1 cells. Further, the 50% ethanol extract from I. chinensis inhibited the neuraminidase (NA) activity of the H6N1 virus. These findings provide important information for exploitation and utilization of I. chinensis in treatment of influenza infection.