Two New 4‐Hydroxyisoflavanes from the Root of Codonopsis cordifolioidea and Their Anti‐virus Activities

Two new 4‐hydroxyisoflavanes, cordifoliflavanes A and B (1 and 2), were isolated from the roots of Codonopsis cordifolioidea. Their structures were elucidated by spectroscopic methods, including extensive 1D‐ and 2D‐NMR techniques. Compounds 1 and 2 were tested for their anti‐HIV‐1 activities and anti‐tobacco mosaic virus activities. The results showed that compounds 1 and 2 have modest anti‐HIV‐1 activities and anti‐tobacco mosaic virus activities, respectively.     

Design of Sensitive Biocompatible Quantum‐Dots Embedded in Mesoporous Silica Microspheres for the Quantitative Immunoassay of Human Immunodeficiency Virus‐1 Antibodies

A novel sandwich‐type electrochemiluminescence (ECL) immunosensor was developed to enable the sensitive detection of HIV‐1 antibodies. This system incorporated mesoporous silica (mSiO₂) complexed with quantum dots (QDs) and nano‐gold particles, which were assembled to enhance signal detection. Magnetic beads were used by immobilizing the secondary anti‐IgG antibody. This was first employed to capture HIV‐1 antibody (Ab) to form a Fe₃O₄/anti‐IgG/Ab complex. A high loading and signal‐enhanced nanocomposite (hereafter referred to as Au‐mSiO₂‐CdTe) was used as a HIV‐1 antigen label. The Au‐mSiO₂‐CdTe nanocomposite was conjugated with the Fe₃O₄/anti‐IgG/Ab complex to form an immunocomplex (hereafter referred to as Fe₃O₄/anti‐IgG/Ab/HIV‐1/CdTe‐mSiO₂‐Au). This complex could be further separated by an external magnetic field to produce ECL signals. Due to the large specific surface area and pore volume of mSiO₂, the loading of the CdTe QDs was markedly increased. Thus, the loaded QDs released a powerful chemiluminescent signal with a concordantly increased sensitivity of the immunosensor. The immunosensor was highly sensitive, and displayed a linear range of responses for HIV‐1 antibody across a dilution range of 1 : 1500 through 1 : 50 with the detection limit of 1 : 4500. The immunoassay can be a promising candidate in early diagnosis of HIV infection.     

Fast parallel detection of feline panleukopenia virus DNA by multi‐channel microchip electrophoresis with programmed step electric field strength

A multi‐channel microchip electrophoresis using a programmed step electric field strength (PSEFS) method was investigated for fast parallel detection of feline panleukopenia virus (FPV) DNA. An expanded laser beam, a 10× objective lens, and a charge‐coupled device camera were used to simultaneously detect the separations in three parallel channels using laser‐induced fluorescence detection. The parallel separations of a 100‐bp DNA ladder were demonstrated on the system using a sieving gel matrix of 0.5% poly(ethylene oxide) (M_r = 8 000 000) in the individual channels. In addition, the PSEFS method was also applied for faster DNA separation without loss of resolving power. A DNA size marker, FPV DNA sample, and a negative control were simultaneously analyzed with single‐run and one‐step detection. The FPV DNA was clearly distinguished within 30 s, which was more than 100 times faster than with conventional slab gel electrophoresis. The proposed multi‐channel microchip electrophoresis with PSEFS was demonstrated to be a simple and powerful diagnostic method to analyze multiple disease‐related DNA fragments in parallel with high speed, throughput, and accuracy.     

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.     

利用无标记的分子信标及核酸染料SYBR Green Ⅰ检测乙肝病毒

本文以野生型的乙型肝炎病毒(HBV)核酸片段为研究对象,利用无标记的分子信标及核酸染料SYBR Green I,建立了一种高灵敏、高选择性的特定序列核酸检测方法.在优化条件下,目标DNA浓度为4×10-11~400×10-11 mol/L之间时,SYBR Green I的荧光强度(ΔI)与目标DNA的浓度(C)具有良好的线性关系,其拟合的回归方程为ΔI=1.9556 C+31.4659(R2=0.9956),方法检测限(3ζ)为2×10-11 mol/L.该方法操作简单、检测速度快、灵敏度高、重现性好、检出限低.利用该方法,结合不对称PCR技术,实现了对HBV的定量检测.     

Early detection of viral DNA in breast cancer using fingered aluminium interdigitated electrode modified by Streptavidin-biotin tetravalent complex

Human Mammary Tumor Virus (HMTV) or Mouse Mammary Tumor Virus holds similarity as an endogenous onco-retrovirus belongs to retroviridae family, predominantly infects the epithelial cell of human as well as mouse. With the recognition of nano-biosensor in nanotechnology, ideal interdigitated electrode (IDE) was genuinely performed for HMTV detection. Aluminium enriched IDE (AlIDE) was fabricated for high performance detection with a cost-effective photolithography technique. In this research, (3-glycidyloxypropyl) trimethoxysilane refined platform was selected to detect the conductivity with HMTV target DNA interaction on the designed AlIDE. Strong binding affinity of streptavidin-biotin with target DNA enhanced the sensitivity by empowering higher number of HMTV probe and target complementation on sensing surface. Furthermore, the target DNA was immobilized on probe modified AlIDE and a quantitative value of 100 aM attained as a lowest detection. A linear with dose-dependent duplex formation was shown with the regression coefficient value of 0.964. Negative control has shown insignificant detection at 10 pM, which justifies the higher fold discrimination with specificity. The excellence of AlIDE performance in detection of HMTV may pave the way for more verification on other diseases.     

Revealing the Cell Entry Dynamic Mechanism of Single Rabies Virus Particle

The rabies virus is a neurotropic virus that causes fatal diseases in humans and animals. Although studying the interactions between a single rabies virus and the cell membrane is necessary for understanding the pathogenesis, the internalization dynamic mechanism of single rabies virus in living cells remains largely elusive. Here, we utilized a novel force tracing technique based on atomic force microscopy(AFM) to record the process of single viral entry into host cell. We revealed that the force of the rabies virus internalization distributed at (65±25) pN, and the time was identified by two peaks with spacings of (237.2±59.1) and (790.3±134.4) ms with the corresponding speed of 0.12 and 0.04 μm/s, respectively. Our results provide insight into the effects of viral shape during the endocytosis process. This report will be meaningful for understanding the dynamic mechanism of rabies virus early infection.     

Prediction of African Swine Fever Virus Inhibitors by Molecular Docking-Driven Machine Learning Models

African swine fever virus (ASFV) causes a highly contagious and severe hemorrhagic viral disease with high mortality in domestic pigs of all ages. Although the virus is harmless to humans, the ongoing ASFV epidemic could have severe economic consequences for global food security. Recent studies have found a few antiviral agents that can inhibit ASFV infections. However, currently, there are no vaccines or antiviral drugs. Hence, there is an urgent need to identify new drugs to treat ASFV. Based on the structural information data on the targets of ASFV, we used molecular docking and machine learning models to identify novel antiviral agents. We confirmed that compounds with high affinity present in the region of interest belonged to subsets in the chemical space using principal component analysis and k-means clustering in molecular docking studies of FDA-approved drugs. These methods predicted pentagastrin as a potential antiviral drug against ASFVs. Finally, it was also observed that the compound had an inhibitory effect on AsfvPolX activity. Results from the present study suggest that molecular docking and machine learning models can play an important role in identifying potential antiviral drugs against ASFVs.     

Pharmacological Activities of Aminophenoxazinones

Aminophenoxazinones are degradation products resulting from the metabolism of different plant species, which comprise a family of natural products well known for their pharmacological activities. This review provides an overview of the pharmacological properties and applications proved by these compounds and their structural derivatives during 2000–2021. The bibliography was selected according to our purpose from the references obtained in a SciFinder database search for the Phx-3 structure (the base molecule of the aminophenoxazinones). Compounds Phx-1 and Phx-3 are among the most studied, especially as anticancer drugs for the treatment of gastric and colon cancer, glioblastoma and melanoma, among others types of relevant cancers. The main information available in the literature about their mechanisms is also described. Similarly, antibacterial, antifungal, antiviral and antiparasitic activities are presented, including species related directly or indirectly to significant diseases. Therefore, we present diverse compounds based on aminophenoxazinones with high potential as drugs, considering their levels of activity and few adverse effects.     

Overview of cationic phthalocyanines for effective photoinactivation of pathogenic microorganisms

Phthalocyanine (Pc) dyes are photoactive compounds that can absorb and emit light in a large range of the UV–vis spectrum, with recognized potential for medical applications. Considering the low solubility of Pc macrocycles in water, it is important to use cationic symptoms on their skeleton to improve their amphiphilicity for biomedical applications. The use of suitable pyridinium groups on Pc is a good strategy to solve this drawback and make them more eff ;ective to photoinactivate microorganisms via a photodynamic inactivation (PDI) approach. This review focuses the synthesis of quaternized Pc dyes, their photophysical and photochemical properties, and their antimicrobial photoinactivation efficiency. This innovative study compares, for the first time, different cationic moieties on Pc taking into account the efficiency of singlet oxygen (¹O₂), quantum yield (Φ_Δ) generation, fluorescence quantum yield (Φ_F), (photo)stability, light irradiation type (visible/white and/or red light), maximized overlapped absorption effect of Pc (S- and/or Q-band) vs light system irradiation type, and water solubility (n-octanol/water partition coefficient, P_o/w), when these parameters are determined and provided in the multidisciplinary reports. This approach is also relevant to conjugate free-base (H₂Pc) and metalated phthalocyanines (MPc, M = Zn²⁺, Mg²⁺, In³⁺, Ga³⁺, Ge³⁺, Si⁴⁺, etc.) with aromatic or aliphatic substituents linked by N, O or S atoms on the peripheral or axial positions of the Pc structures, such as e.g. (methoxy, oxy, or thio)pyridinium, ammonium, or benzimidazolium units, etc. Here, the influence of the structural peripheral (α- and/or β-position of Pc) or axial substituents type, number and positive charge position that can affect the PDI process will be analysed. These aspects are important to design versatile molecules that can interact with pathogenic microorganisms of variable size, subcellular architecture, biochemical composition, and susceptibility to externally added chemical agents. This review highlights the important developments of several modifications of cationic Pc dyes for the PDI of microorganisms, such as pathogenic bacteria, fungi, and virus.