scholarly journals Study on rapid screening technology of antisense oligonucleotides for SARS-CoV-2

2021 ◽  
Author(s):  
Huawei Shen
Keyword(s):  
Nucleic Acid ◽  
Human Genome ◽  
Antisense Oligonucleotides ◽  
Structural Characteristics ◽  
Inhibitory Effect ◽  
Experimental Results ◽  
Rapid Screening ◽  
Screening Technology

Abstract According to the structural characteristics of SARS-CoV-2 nucleic acid,SARS-CoV-2 genomes were virtually segmented. After comparing with human genome, 44707 SARS-CoV-2 genomes and 26 primates' genomes, 18 antisense oligonucleotides sequences were selected. Experimental results show that the combined inhibitory effect reaches 100% .

scholarly journals Study on rapid screening technology of antisense oligonucleotides for SARS-CoV-2

2021 ◽  
Author(s):  
Huawei Shen
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
Structural Characteristics ◽  
Inhibitory Effect ◽  
Rapid Screening ◽  
Short Term ◽  
Physical Isolation ◽  
The World ◽  
Actual Use ◽  
Screening Technology

Abstract According to the structural characteristics of SARS-CoV-2 nucleic acid,SARS-CoV-2 genomes were virtually segmented.After comparing with human genome,44707 SARS-CoV-2 genomes and 26 primates' genomes, 19 antisense oligonucleotides sequences were selected.Experimental results show that the combined inhibitory effect reaches 100% . Significance statement：Currently, effective methods of controlling the spread of SARS-CoV-2 are very limited, only physical isolation and vaccination.Although physical isolation can achieve some short-term results, but can not fundamentally solve the problem of epidemic spread.The time between the development of a vaccine and its actual use is very long.It often happens that the vaccine is developed successfully, but the epidemic situation is beyond control.If a mutant strain emerges, it will take longer.I hope that the rapid screening technology of SARS-CoV-2 antisense oligonucleotides will light up new hope for the future of mankind and contribute oriental wisdom to the world.

In vitro evaluation of hexitol nucleic acid antisense oligonucleotides

1999 ◽  
Author(s):  
Arthur Van Aerschot ◽  
Mark Vandermeeren ◽  
Johan Geysen ◽  
Walter Luyten ◽  
Marc Miller ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
In Vitro Evaluation

scholarly journals A study of the binding between radicicol and four proteins by means of spectroscopy and molecular docking

2021 ◽  
pp. 174751982199306
Author(s):  
Ya Gan ◽  
Ning Bai ◽  
Xitong Li ◽  
Shuiting Gao ◽  
Ruiyong Wang
Keyword(s):  
Molecular Docking ◽  
Human Serum ◽  
Serum Protein ◽  
Binding Constant ◽  
Inhibitory Effect ◽  
Experimental Results ◽  
Static Quenching ◽  
Spectroscopic Techniques ◽  
Quenching Process ◽  
Human Serum Protein

The interactions between radicicol and four proteins (catalase, trypsin, pepsin, and human serum protein) are investigated by spectroscopic techniques and molecular docking. A static quenching process is confirmed. The binding constant value between radicicol and human serum protein is the largest among the four proteins. Results reveal changes in the micro-environment of the protein by the addition of radicicol. It is found that radicicol shows an inhibitory effect on the activity of proteins (catalase, trypsin, and pepsin). Molecular docking results are consistent with the thermodynamic experimental results. This work provides clues to the elucidation of the mechanisms of the interactions between radicicol and proteins.

scholarly journals Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

2021 ◽  
Vol 17 ◽  
pp. 622-629
Author(s):  
Naohiro Horie ◽  
Takao Yamaguchi ◽  
Shinji Kumagai ◽  
Satoshi Obika
Keyword(s):  
Nucleic Acid ◽  
Binding Affinity ◽  
Antisense Oligonucleotides ◽  
Modified Oligonucleotides ◽  
Biophysical Properties ◽  
Chemical Modifications ◽  
Antisense Technology ◽  
Strong Affinity ◽  
The Stability

Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine (mC). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -mC toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.

scholarly journals Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug

2021 ◽  
Vol 15 (4) ◽  
pp. e0009276
Author(s):  
Lisa Sanderson ◽  
Marcelo da Silva ◽  
Gayathri N. Sekhar ◽  
Rachel C. Brown ◽  
Hollie Burrell-Saward ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Structural Characteristics ◽  
Research Programme ◽  
Inhibitory Effect ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Neglected Diseases ◽  
Target Candidate Profile

Background Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10–100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations. Methodology To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluation in vitro, quantified pentamidine CNS delivery of a sub-set of formulations in vitro and in vivo, and progressed one pentamidine-Pluronic formulation for further evaluation using an in vivo single dose brain penetration study. Principal Findings Screening pentamidine against 40 CNS targets did not reveal any major neurotoxicity concerns, however, pentamidine had a high affinity for the imidazoline2 receptor. The reduction in insulin secretion in MIN6 β-cells by pentamidine may be secondary to pentamidine-mediated activation of β-cell imidazoline receptors and impairment of cell viability. Pluronic F68 (0.01%w/v)-pentamidine formulation had a similar inhibitory effect on insulin secretion as pentamidine alone and an additive trypanocidal effect in vitro. However, all Pluronics tested (P85, P105 and F68) did not significantly enhance brain exposure of pentamidine. Significance These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.

scholarly journals Efficient Inhibition of SARS-CoV-2 Using Chimeric Antisense Oligonucleotides through RNase L Activation

2021 ◽  
Author(s):  
Xiaoxuan Su ◽  
Wenxiao Ma ◽  
Boyang Cheng ◽  
Qian Wang ◽  
Zefeng Guo ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antisense Oligonucleotides ◽  
Target Recognition ◽  
Vero Cells ◽  
Rnase L ◽  
Rna Targets ◽  
Infection Models ◽  
Antisense Sequence ◽  
Innate Antiviral Response ◽  
Chimeric Oligonucleotides

AbstractThere is an urgent need for effective antiviral drugs to alleviate the current COVID-19 pandemic. Here, we rationally designed and developed chimeric antisense oligonucleotides to degrade envelope and spike RNAs of SARS-CoV-2. Each oligonucleotide comprises a 3’ antisense sequence for target recognition and a 5’-phosphorylated 2’-5’ poly(A)4 for guided ribonuclease L (RNase L) activation. Since RNase L can potently cleave single strand RNA during innate antiviral response, the improved degradation efficiency of chimeric oligonucleotides was twice as much as classic antisense oligonucleotides in Vero cells, for both SARS-CoV-2 RNA targets. In pseudovirus infection models, one of chimeric oligonucleotides targeting spike RNA achieved potent and broad-spectrum inhibition of both SARS-CoV-2 and its recently reported N501Y and/or ΔH69/ΔV70 mutants. These results showed that the constructed chimeric oligonucleotides could efficiently degrade pathogenic RNA of SARS-CoV-2 facilitated by immune activation, showing promising potentials as antiviral nucleic acid drugs for COVID-19.

scholarly journals Effect of kinetin on nucleic acid synthesis in senescing and young leaves in Brassica oleracea L. var. gongylodes L.

2015 ◽  
Vol 44 (4) ◽  
pp. 553-565
Author(s):  
J. Legocka ◽  
A. Szweykowska
Keyword(s):  
Molecular Weight ◽  
Nucleic Acid ◽  
Acid Synthesis ◽  
Inhibitory Effect ◽  
Rrna Synthesis ◽  
Low Molecular Weight ◽  
Chlorophyll B ◽  
Mature Leaves ◽  
Young Leaves ◽  
Brassica Oleracea L

In detached kohlrabi leaves senescing in the dark, the decrease in chlorophyll to was more pronounced than in chlorophyll a. The retardation by kinetin of the chlorophyll loss was also markedly stronger in the case of chlorophyll b. Using the fractionation of nucleic acids on polyacrylamide gels it has been shown that during leaf senescence the level of all RNA species decreased, whereas the amount of DNA was more or less constant. In the presence of kinetin, the loss of RNA was inhibited and the incorporation of precursor into the cytoplasmic rRNA as well as into low molecular weight RNA species was supported. Chloroplast rRNA synthesis has not been detected in mature leaves and kinetin showed no effect in this respect. In young expanding leaves detached and kept in light, the synthesis of cytoplasmic rRNA was strongly stimulated by kinetin, whereas in the case of Chloroplast rRNA only an inhibitory effect of kinetin could be found. The results suggest that the cytokinins are primarily involved in processes of the synthesis of cytoplasmic rRNA and low molecular RNA fractions, and in this way affect the development of plastids, in particular the course of their senescence.

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