• Title/Summary/Keyword: replication strategy

Search Result 64, Processing Time 0.022 seconds

Finding and Characterization of Viral Nonstructural Small Protein in Prospect Hill Virus Infected Cell

  • Nam, Ki-Yean;Chung, Dong-Hoon;Choi, Je-Won;Lee, Yun-Seong;Lee, Pyung-Woo
    • The Journal of Korean Society of Virology
    • /
    • v.29 no.4
    • /
    • pp.221-233
    • /
    • 1999
  • Prospect Hill Virus (PHV) is the well known serotype of hantavirus, a newly established genus in family Bunyaviridae. Extensive studies have upheld the original view of PHV genetics with three genes such as nucleocapsid (N) protein, envelope proteins (G1, G2) and RNA dependent RNA polymerase. In this study, we report the existence of additional gene that is encoded in an overlapping reading frame of the N protein gene within S genome segment of PHV. This gene is expected to encode a nonstructural small (NSs) protein and it seems to be only found in PHV infected cell. The presence and synthesis of NSs protein could be demonstrated in the cell infected with PHV using anti-peptide sera specific to the predicted amino acid sequence deduced from the second open reading frame. Ribosomal synthesis of this protein appears to occur at AUG codon at the 83rd base of S genome segment, downstream of N protein initiation codon. This protein is small in size (10.4 KDa) and highly basic in nature. The expression strategy of NSs protein appears that a signal mRNA is used to translate both N and NSs protein in PHV infected cell. 10 KDa protein in virus infected cell lysates can bind to mimic dsRNA. This fact strongly suggests that NSs protein may be involved in virus replication on late phase of viral life cycle.

  • PDF

Virtual Screening for Potential Inhibitors of NS3 Protein of Zika Virus

  • Sahoo, Maheswata;Jena, Lingaraja;Daf, Sangeeta;Kumar, Satish
    • Genomics & Informatics
    • /
    • v.14 no.3
    • /
    • pp.104-111
    • /
    • 2016
  • Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.

Pathological Impact on the Phyllosphere Microbiota of Artemisia argyi by Haze

  • Zhang, Yu-Zhu;Jiang, De-Yu;Zhang, Chi;Yang, Kun;Wang, Huai-Fu;Xia, Xiu-Wen;Ding, Wei-Jun
    • Journal of Microbiology and Biotechnology
    • /
    • v.31 no.4
    • /
    • pp.510-519
    • /
    • 2021
  • The pathological impact of haze upon the phyllosphere microbiota awaits investigation. A moderate degree of haze environment and a clean control were selected in Chengdu, China. Artemisia argyi, a ubiquitously distributed and extensively applied Chinese herb, was also chosen for experiment. Total genome DNA was extracted from leaf samples, and for metagenome sequencing, an Illumina HiSeq 2500 platform was applied. The results showed that the gene numbers of phyllosphere microbiota derived from haze leaves were lower than those of the clean control. The phyllosphere microbiota derived from both haze and clean groups shared the same top ten phyla; the abundances of Proteobacteria, Actinomycetes and Anorthococcuso of the haze group were substantially increased, while Ascomycetes and Basidiomycetes decreased. At the genus level, the abundances of Nocardia, Paracoccus, Marmoricola and Knoelia from haze leaves were markedly increased, while the yeasts were statistically decreased. KEGG retrieval demonstrated that the functional genes were most annotated to metabolism. An interesting find of this work is that the phyllosphere microbiota responsible for the synthesis of primary and secondary metabolites in A. argyi were significantly increased under a haze environment. Relatively enriched genes annotated by eggNOG belong to replication, recombination and repair, and genes classified into the glycoside hydrolase and glycosyltransferase enzymes were significantly increased. In summary, we found that both structure and function of phyllosphere microbiota are globally impacted by haze, while primary and secondary metabolites responsible for haze tolerance were considerably increased. These results suggest an adaptive strategy of plants for tolerating and confronting haze damage.

Potential of Hanjeli (Coix lacryma-jobi) essential oil in preventing SARS-CoV-2 infection via blocking the Angiotensin Converting Enzyme 2 (ACE2) receptor

  • Diningrat, Diky Setya;Sari, Ayu Nirmala;Harahap, Novita Sari;Kusdianti, Kusdianti
    • Journal of Plant Biotechnology
    • /
    • v.48 no.4
    • /
    • pp.289-303
    • /
    • 2021
  • Covid-19 is an ongoing pandemic as we speak in 2022. This infectious disease is caused by the SARS-CoV-2 virus, which infects cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface. Thus, strategies that inhibit the binding of SARS-CoV-2 to the ACE2 receptor can stop this contagion. Hanjeli (Coix lacryma-jobi) essential oil contains many bioactive compounds, including dodecanoic acid; tetradecanoic acid; 7-Amino-8-imino-2-(2-imino-2H-chromen-3-yl); and 1,5,7,10-tetraaza-phen-9-one. These compounds suppress viral replication and may prevent Covid-19. Accordingly, this study assessed whether, these four limonoid compounds can block the ACE2 receptor. To this end, their physicochemical properties were predicted using Lipinski's "rule of five" on the SwissADME website, and their toxicity was assessed using the online tools ProTox and pkCSM. Additionally, their interactions with the ACE2 receptor were predicted via molecular docking using Autodock Vina. All the four compounds satisfied the "rule of five" and tetradecanoic acid was predicted to have a higher affinity than the comparison compound remdesivir and the original ligand of ACE2. Molecular docking results suggested that the compounds from hanjeli essential oil interact with the active site of the ACE2 receptor similarly as the original ligand and remdesivir. In conclusion, hanjeli essential oil contains compounds predicted hinder the interaction of SARS-CoV-2 with the ACE2 receptor. Accordingly, our data may facilitate the development of a phytomedical strategy against SARS-CoV-2 infection.

Expression of FMD virus-like particles in yeast Hansenula polymorpha and immunogenicity of combine with CpG and aluminum adjuvant

  • Jianhui Zhang;Jun Ge;Juyin Li;Jianqiang Li;Yong Zhang;Yinghui Shi;Jiaojiao Sun;Qiongjin Wang;Xiaobo Zhang;Xingxu Zhao
    • Journal of Veterinary Science
    • /
    • v.24 no.1
    • /
    • pp.15.1-15.13
    • /
    • 2023
  • Background: Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. Objectives: The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. Methods: BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. Results: The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4+ T cells were observed in mice immunized with VLPs. Conclusions: The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.

Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target

  • Jaewoo Hong;Hyunjhung Jhun;Yeo-Ok Choi;Afeisha S. Taitt;Suyoung Bae;Youngmin Lee;Chang-seon Song;Su Cheong Yeom;Soohyun Kim
    • IMMUNE NETWORK
    • /
    • v.21 no.1
    • /
    • pp.8.1-8.17
    • /
    • 2021
  • The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.

Hepatitis C Virus Core Protein Activates p53 to Inhibit E6-associated Protein Expression via Promoter Hypermethylation (C형 간염바이러스 코어 단백질에 의한 p53 활성화와 프로모터 과메틸화를 통한 E6AP 발현 억제)

  • Kwak, Juri;Jang, Kyung Lib
    • Journal of Life Science
    • /
    • v.28 no.9
    • /
    • pp.1007-1015
    • /
    • 2018
  • The E6-associated protein (E6AP) is known to induce the ubiquitination and proteasomal degradation of HCV core protein and thereby directly impair capsid assembly, resulting in a decline in HCV replication. To counteract this anti-viral host defense system, HCV core protein has evolved a strategy to inhibit E6AP expression via DNA methylation. In the present study, we further explored the mechanism by which HCV core protein inhibits E6AP expression. HCV core protein upregulated both the protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b to inhibit E6AP expression via promoter hypermethylation in HepG2 cells but not in Hep3B cells, which do not express p53. Interestingly, p53 overexpression alone in Hep3B cells was sufficient to activate DNMTs in the absence of HCV core protein and thereby inhibit E6AP expression via promoter hypermethylation. In addition, upregulation of p53 was absolutely required for the HCV core protein to inhibit E6AP expression via promoter hypermethylation, as evidenced by both p53 knockdown and ectopic expression experiments. Accordingly, levels of the ubiquitinated forms of HCV core protein were lower in HepG2 cells than in Hep3B cells. Based on these observations, we conclude that HCV core protein evades ubiquitin-dependent proteasomal degradation in a p53-dependent manner.

Inhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA molecules

  • Li, Zhi;He, Ming-Liang;Yao, Hong;Dong, Qing-Ming;Chen, Yang-Chao;Chan, Chu-Yan;Zheng, Bo-Jian;Yuen, Kwok-Yung;Peng, Ying;Sun, Qiang;Yang, Xiao;Lin, Marie C.;Sung, Joseph J.Y.;Kung, Hsiang-Fu
    • BMB Reports
    • /
    • v.42 no.1
    • /
    • pp.59-64
    • /
    • 2009
  • Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.

Dissemination and Utilization of Growing-up Skills Program (성장기술 프로그램의 보급 및 활용에 관한 연구)

  • Choi, Myung-Min
    • Korean Journal of Social Welfare
    • /
    • v.52
    • /
    • pp.89-115
    • /
    • 2003
  • While many social work studies has focused on the development of practice intervention and demonstration of the efficacy, little attention has been given to the way how the results can be disseminated and utilized in practice area. But attempts to bridge the research-practice gap empathize importance of dissemination and utilization including knowledge utilization, innovation diffusion, information dissemination, program replication, and technology transfer etc. In this recognition, this study that focused on the process after development of program tried to search and analyze the real disseminating process and utilization state with applying Growing-up Skills Program(GUSP) developed and disseminated by this researcher. For the purpose, theories and models for program diffusion were reviewed, and dissemination & utilization of GUSP was analyzed on the 'Herie & Martin's model' with retrospective perspectives. Through this tracer study, these were confirmed or founded as problems of GUSP in disseminating process : lack of specific strategy for the dissemination ; unplanned coping due to little preparation ; and unclear and insufficient understanding of the target system in the beginning stage of dissemination. And followings are suggested for the improvement of social work program dissemination & utilization in the field: to conduct diffusion process on the basis of a proper model; to consider integrative relationship between D&D and dissemination & utilization ; to endeavor for collecting feed back from the field ; and to reinforce social work education and study related to innovation diffusion. These results showed importance of dissemination & utilization in social work and utility of GUSP despite of several limitations. More concerns of dissemination & utilization are needed for the integration of research and practice in Korean social work.

  • PDF

Design and Evaluation of a Fuzzy Logic based Multi-hop Broadcast Algorithm for IoT Applications (IoT 응용을 위한 퍼지 논리 기반 멀티홉 방송 알고리즘의 설계 및 평가)

  • Bae, Ihn-han;Kim, Chil-hwa;Noh, Heung-tae
    • Journal of Internet Computing and Services
    • /
    • v.17 no.6
    • /
    • pp.17-23
    • /
    • 2016
  • In the future network such as Internet of Things (IoT), the number of computing devices are expected to grow exponentially, and each of the things communicates with the others and acquires information by itself. Due to the growing interest in IoT applications, the broadcasting in Opportunistic ad-hoc networks such as Machine-to-Machine (M2M) is very important transmission strategy which allows fast data dissemination. In distributed networks for IoT, the energy efficiency of the nodes is a key factor in the network performance. In this paper, we propose a fuzzy logic based probabilistic multi-hop broadcast (FPMCAST) algorithm which statistically disseminates data accordingly to the remaining energy rate, the replication density rate of sending node, and the distance rate between sending and receiving nodes. In proposed FPMCAST, the inference engine is based the fuzzy rule base which is consists of 27 if-then rules. It maps input and output parameters to membership functions of input and output. The output of fuzzy system defines the fuzzy sets for rebroadcasting probability, and defuzzification is used to extract a numeric result from the fuzzy set. Here Center of Gravity (COG) method is used to defuzzify the fuzzy set. Then, the performance of FPMCAST is evaluated through a simulation study. From the simulation, we demonstrate that the proposed FPMCAST algorithm significantly outperforms flooding and gossiping algorithms. Specially, the FPMCAST algorithm has longer network lifetime because the residual energy of each node consumes evenly.