病毒感染群体动力学模型分析

本文构建并讨论了一类病毒感染的群体动力学模型,得到了模型存在轨道稳定周 期解的充分条件,较好地解释了在病毒持续感染者体内观察到的病毒载量波动现象.     

Chemical composition of the volatile oil from Cynanchum stauntonii and its activities of anti-influenza virus

The volatile oil of the roots of Cynanchum stauntonii was examined by gas chromatography–mass spectrometry (GC–MS). Thirty-eight constituents were identified. (E,E)-2,4-Decadienal, 3-efhyl-4-methypentanol, 5-pentyl-3H-furan-2-one, (E,Z)-2,4-decadienal and 2(3H)-furanone,dihydro-5-pentyl were found to be the major components. The volatile oil exhibited the activities against influenza virus in vitro (IC₅₀s = 64 μg/ml). In in vivo experiment, it prevented influenza virus-induced deaths in a dose-dependent manner.     

A structural and energetics analysis of the binding of a series of N-acetylneuraminic-acid-based inhibitors to influenza virus sialidase

Summary A molecular dynamics/energy-minimisation protocol has been used to analyse the structural and energetic effects of functional group substitution on the binding of a series of C4-modified 2-deoxy-2,3-didehydro-N-acetylneuraminic acid inhibitors to influenza virus sialidase. Based on the crystal structure of sialidase, a conformational searching protocol, incorporating multiple randomisation steps in a molecular dynamics simulation was used to generate a range of minimum-energy structures. The calculations were useful for predicting the number, location, and orientation of structural water molecules within protein-ligand complexes. Relative binding energies were calculated for the series of complexes using several empirical molecular modelling approaches. Energies were computed using molecular-mechanics-derived interactions as the sum of pairwise atomic nonbonded energies, and in a more rigorous manner including solvation effects as the change in total electrostatic energy of complexation, using a continuum-electrostatics (CE) approach. The CE approach exhibited the superior correlation with observed affinities. Both methods showed definite trends in observed and calculated binding affinities; in both cases inhibitors with a positively charged C4 substituent formed the tightest binding to the enzyme, as observed experimentally.This paper is based on a presentation given at the 14th Molecular Graphics and Modelling Society Conference, held in Cairns, Australia, August 27–September 1, 1995.Presently on a visiting postdoctoral fellowship in the Department of Biomolecular Structure, Glaxo Research & Development Ltd, Greenford, Middlesex UB6 OHE, U.K.     

Synthesis and Inhibitory Activity Against Epstein-Barr Virus of Some New 1,2,3,4-Tetrahydropyrimidine-2-thiones

1,2,3,4-Tetrahydropyrimidine-2-thiones 4a–n were synthesized through the reaction of aromatic aldehydes 1a–n , ethyl acetoacetate (2) and thiourea ( 3) . The structures of all newly synthesized heterocyclic compounds elucidated by the use of IR, ¹H NMR, mass spectra, and elemental analyses. The inhibitory activity against the Epstein-Barr Virus early antigen (EBA-VA) of all newly synthesized heterocyclic compounds were evaluated.     

Design,synthesis and anti-influenza virus activities of terminal modified antisense oligonucleotides

Four novel terminal modified antisense oligonucleotides (ODNs) were designed, synthesized and tested for their anti-influenza virus activity. Initial biological studies indicated that lipophilic and rimantadin emodificated Flutide exhibited more potent anti-H1N1 activity than Flutide. Among them, lipophilic modificated ODN (Flutide-I) showed the most antiviral activity. The EC₅₀ value of Flutide-I for inhibiting H1N1 induced cytopathic effect (CPE) and H1N1 RNA were respectively (0.26 ± 0.16) μM and (0.11 ± 0.03) μM. The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds with the concentrations up to 20 μM.     

Surface-Enhanced Raman Spectroscopy (SERS) for characterization SARS-CoV-2

We used SERS with silver nanoparticles (AgNPs) as the active substrate to develop a, simple, quick, and accurate method for the detection and characterization SARS-CoV-2 without the need for RNA isolation and purification. Inactivated SARS-CoV-2 was used. The SERS signals were more than 10⁵ times enhanced than the normal Raman (NR) spectra. The SERS spectra of SARS-CoV-2 fingerprint revealed pronounced intensity signals of nucleic acids; aromatic amino acid side chains: 1007 cm^?1 (Phe marker), 1095 cm^?1 (CN and PO₂^? markers), 1580 cm^?1 (Tyr, Trp markers). Vibrations of the protein main chain: 1144 cm^?1 (CN and NH₂ markers), 1221 cm^?1 (CN and NH markers), 1270 cm^?1 (NH₂ marker), 1453 cm^?1 (CHCH₂ marker). All of these biomolecules could be adsorbed on the AgNPs surface's dense hot patches. The intensity of the SERS band varied with the concentration of SARS-CoV-2, with a virus detection limit of less than 10³ vp/mL and RSDs of 20 %.     

The enormity of the zinc deficiency problem and available solutions; an overview

The societal cost of micronutrient deficiency (MND) or the “hidden hunger” is in millions of dollars/year, reducing the GDP of some countries by as much as 11%. Zn is an important micronutrient for both plants and animals. An estimated 17% of the world population, or around 1.1 billion people, are at the risk of zinc (Zn) deficiency. The deficiency has been related to adverse pregnancy outcomes, stunted growth, premature deaths, immune system dysfunctions, neuro-behavioral disorders, and recently with the failure to recover from COVID-19. These health risks associated with Zn deficiency have compelled FAO and WHO to recommend Zn fortification of diet. Correcting Zn deficiency is a challenge due to several reasons. Close to half of the agricultural soils are Zn deficient, and chemical Zn fertilizers are costly and ineffective. Developing Zn-rich crops through plant breeding and genetic engineering is challenging. Zn-dense diet is costly and cannot be implemented in the low-income region most affected by Zn deficiency. Lack of consensus among regulatory bodies on defining and diagnosing Zn deficiency in plants and Humans. Awareness and other sociocultural issues. Among the most important available solutions are zinc biofortification of the cereal crops, use of zinc biofertilizers, development of Zn-efficient crops with reduced phytate content. The use of Zn supplements, dietary modification, and diversification, especially with fish, are proposed as the most accessible and affordable solutions. Awareness programs in areas suffering the most from Zn deficiency are required. Despite the suggestions from FAO and WHO, global efforts to combat Zn deficiency matching those for combating diseases like HIV are not in place. Coordinated efforts of the international community, especially policy-makers, agricultural scientists, dieticians, physicians, and others, are required to address the issue of hidden hunger.     

Structure-based virtual screening of influenza virus RNA polymerase inhibitors from natural compounds: Molecular dynamics simulation and MM-GBSA calculation

The resistances of matrix protein 2 (M2) protein inhibitors and neuraminidase inhibitors for influenza virus have attracted much attention and there is an urgent need for new drug. The antiviral drugs that selectively act on RNA polymerase are less prone to resistance and possess fewer side effects on the patient. Therefore, there is increased interest in screening compounds that can inhibit influenza virus RNA polymerase. Three natural compounds were found by using molecular docking-based virtual screening, which could bind tightly within the polymerase acidic protein-polymerase basic protein 1 (PA-PB1) subunit of influenza virus polymerase. Firstly, their drug likeness properties were evaluated, which showed that the hepatotoxicity values of all the three compounds indicating they had less or no hepatotoxicity, and did not have the plasma protein biding (PPB) ability, the three compounds needed to be modified in some aspects, like bulky molecular size. The stability of the complexes of PA-hits was validated through molecular dynamics (MD) simulation, revealing compound 2 could form more stable complex with PA subunit. The torsional conformations of each rotatable bond of the ligands in PA subunit were also monitored, to investigate variation in the ligand properties during the simulation, compound 3 had fewer rotatable bonds, indicating that the molecule had stronger rigidity. The bar charts of protein–ligand contacts and contacts over the course of trajectory showed that four key residues (Glu623, Lys643, Asn703 and Trp706) of PA subunit that participated in hydrogen-bond, water bridge and hydrophobic interactions with the hit compounds. Finally, the binding free energy and contributed energies were calculated by using MM-GBSA method. Out of the three compounds, compound 1 showed the lowest total binding free energy. Among all the interactions, the contribution of the covalent binding and the van der Waals energy were more than other items, compound 1 formed more stable hydrogen bonds with the residues of PA subunit binding pocket. This study smoothed the path for the development of novel lead compounds with improved binding properties, high drug likeness, and low toxicity to humans for the treatment of influenza, which provided a good basis for further research on novel and effective influenza virus PA-PB1 interaction inhibitors.     

A network-based pharmacology study of active compounds and targets of Fritillaria thunbergii against influenza

Seasonal and pandemic influenza infections are serious threats to public health and the global economy. Since antigenic drift reduces the effectiveness of conventional therapies against the virus, herbal medicine has been proposed as an alternative. Fritillaria thunbergii (FT) have been traditionally used to treat airway inflammatory diseases such as coughs, bronchitis, pneumonia, and fever-based illnesses. Herein, we used a network pharmacology-based strategy to predict potential compounds from Fritillaria thunbergii (FT), target genes, and cellular pathways to better combat influenza and influenza-associated diseases. We identified five compounds, and 47 target genes using a compound-target network (C-T). Two compounds (beta-sitosterol and pelargonidin) and nine target genes (BCL2, CASP3, HSP90AA1, ICAM1, JUN, NOS2, PPARG, PTGS1, PTGS2) were identified using a compound-influenza disease target network (C-D). Protein-protein interaction (PPI) network was constructed and we identified eight proteins from nine target genes formed a network. The compound-disease-pathway network (C-D-P) revealed three classes of pathways linked to influenza: cancer, viral diseases, and inflammation. Taken together, our systems biology data from C-T, C-D, PPI and C-D-P networks predicted potent compounds from FT and new therapeutic targets and pathways involved in influenza.