• 통합자연과학논문집
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• 제6권3호
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• pp.138-142
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• 2013

The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of the virus into the host cells. The crucial role of the glycoprotein suggests gp120 as potential drug target for the future antiviral therapies. Identification of the binding mode of small drug like compounds has been an important goal in drug design. In the current study we attempt to propose binding mode of indole derivatives in the binding pocket of gp120. These derivatives are reported to inhibit HIV-1 by acting as attachment inhibitors that bind to gp120 and prevent the gp120-CD4 interaction and thus inhibit the infectivity of HIV-1. To elucidate the molecular basis of the small molecules interactions to inhibit the glycoprotein function we employed the molecular docking simulation approach. This study provides insights to elucidate the binding pattern of indole-based gp120 inhibitors and may help in the rational design of novel HIV-1 inhibitors with improved potency.

• IMMUNE NETWORK
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• 제23권4호
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• pp.31.1-31.18
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• 2023

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

• Molecules and Cells
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• 제28권1호
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• pp.57-65
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• 2009

CDC48 is a member of the AAA ATPase superfamily. Yeast CDC48 and its mammalian homolog p97 are implicated in diverse cellular processes, including mitosis, membrane fusion, and ubiquitin-dependent protein degradation. However, the cellular functions of plant CDC48 proteins are largely unknown. In the present study, we performed virus-induced gene silencing (VIGS) screening and found that silencing of a gene encoding a tobacco CDC48 homolog, NgCDC48, resulted in severe abnormalities in leaf and shoot development in tobacco. Furthermore, transgenic tobacco plants (35S:anti-NgCDC48), in which the NgCDC48 gene was suppressed using the antisense RNA method, exhibited severely aberrant development of both vegetative and reproductive organs, resulting in arrested shoot and leaf growth and sterile flowers. Approximately 57-83% of 35S:anti-NgCDC48 plants failed to develop mature organs and died at early stage of development. Scanning electron microscopy showed that both adaxial and abaxial epidermal pavement cells in antisense transgenic leaves were significantly smaller and more numerous than those in wild type leaves. These results indicate that NgCDC48 is critically involved in cell growth and development of tobacco plants. An in vivo targeting experiment revealed that NgCDC48 resides in the endoplasmic reticulum (ER) in tobacco protoplasts. We consider the tantalizing possibility that CDC48-mediated degradation of an as-yet unidentified protein(s) in the ER might be a critical step for cell growth and expansion in tobacco leaves.

• 한국동물위생학회지
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• 제44권4호
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• pp.195-207
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• 2021

Species A rotaviruses (RVAs) replicate and assemble their immature particles within electron dense compartments known as viroplasms, where lipid droplets (LDs) interact with the viroplasm and facilitate viral replication. Despite the importance of LD formation in the life cycle of RVAs, the upstream molecules modulating LD formation remain unclear. This study aimed to find out the role of sterol regulatory element-binding proteins (SREBPs) in reprogramming of LD formation after RVA infection. Here, we demonstrate that RVA infection reprograms the sterol regulatory element-binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells, and that both SREBP-1 and -2 transactivated genes, which are involved in fatty acid and cholesterol biosynthesis, are essential for LD formation. Our results showed that pharmacological inhibition of SREBPs using AM580 and betulin and inhibition of their downstream cholesterol biosynthesis (simvastatin for HMG-CoA reductase) and fatty acid enzymes (TOFA) negatively modulated the intracellular triacylglycerides and cholesterol levels and their resulting LD and viroplasm formations. Interestingly, pharmacological inhibition of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny production. This study identified SREBPs-mediated lipogenic reprogramming in RVA-infected host cells, which facilitates virus replication through LD formation and its interaction with viroplasms, suggesting that SREBPs can be a potential target for the development of efficient and affordable therapeutics against RVA infection.

• 한국미생물·생명공학회지
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• 제39권2호
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• pp.140-145
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• 2011

돼지유행성설사 바이러스(porcine epidemic diarrhea virus: PEDV)는 자돈에게 감염 시 수양성설사를 동반한 급성 장염을 유발하며 매우 높은 폐사율을 보이는 그룹 1 코로나바이러스이다. PEDV는 다른 그룹 1 코로나바이러스와 마찬가지로 숙주 세포에 감염 시 aminopeptidase N (APN)을 세포 수용체로 이용한다고 알려져 있다. 코로나바이러스의 spike(S) 단백질은 숙주세포의 표면에 부착과 관련하여 감염 개시에 있어 중요한 역할을 하는 것으로 알려져 있으며 특히 S 단백질의 S1 도메인은 세포 수용체에 특이적인 결합을 매개하는 수용체 결합 도메인(receptor binding domain: RBD)을 포함하고 있는 것으로 알려져 있다. 이미 많은 코로나바이러스의 RBD의 위치가 확인되어져 있지만 PEDV의 RBD에 대해서는 아직까지 알려진 바가 없다. 본 연구에서는 돼지 APN 수용체와 결합을 매개하는 PEDV의 RBD를 규명하기 위해 S1 도메인을 주형으로 하는 일련의 재조합 truncated variant들을 제작하였고 각각의 truncated들이 실제로 pAPN과의 결합을 이루는지에 대하여 실험을 통해 확인하였다. 그 결과 S1 도메인의 N 말단 부분이 pAPN과의 결합에서 중요한 부위임을 확인할 수 있었다. 본 연구에서 도출된 결과는 향후 PEDV의 S 단백질과 pAPN간의 분자적 상호작용을 이해하는 데에 도움을 줄 것으로 판단된다.

• Natural Product Sciences
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• 제29권2호
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• pp.104-112
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• 2023

COVID-19 caused a catastrophe in human health. People infected with COVID-19 also suffer from various clinical illnesses during and after the infection. The Boerhavia diffusa plant is well known for its antihypertensive activity. ACE-II inhibitors and calcium channel blockers are reported as mechanisms for the antihypertensive activity of B. diffusa phytoconstituents. Various studies have said ACE-II is the virus's binding site to attack host cells. COVID-19 treatment commonly employs a variety of synthetic antiviral and steroidal drugs. As a result, other clinical illnesses, such as hypertension and hyperglycemia, emerge as serious complications. Safe and effective drug delivery is a prime objective of the drug development process. COVID-19 is treated with various herbal treatments; however, they are not widely used due to their low potency. Many herbal plants and formulations are used to treat COVID-19 infection, in which B. diffusa is the most widely used plant. The current study relies on discovering active phytoconstituents with ACE-II inhibitory activity in the B. diffusa plant. As a result, it can be used as a treatment option for patients with COVID-19 and related diseases. Different phytoconstituents of the B. diffusa plant were selected from the reported literature. The activity of phytoconstituents against ACE-II proteins has been studied. Molecular docking and ligand-protein interaction computation tools are used in the in-silico experiment. Physicochemical, drug-likeness, water solubility, lipophilicity, and pharmacokinetic parameters are used to evaluate phytoconstituents. Liriodenine has the best drug-likeness, bioactivity, and binding score characteristics among the selected ligands. The in-silico study aims to find the therapeutic potential of B. diffusa phytoconstituents against ACE-II. Targeting ACE-II also shows an effect against SARS-CoV-2. It can serve as a rationale for designing a drug for patient infected with COVID-19 and associated diseases.

• Molecules and Cells
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• 제43권5호
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• pp.469-478
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• 2020

Hepatitis C virus (HCV) propagation is highly dependent on cellular proteins. To identify the host factors involved in HCV propagation, we previously performed protein microarray assays and identified the LIM and SH3 domain protein 1 (LASP-1) as an HCV NS5A-interacting partner. LASP-1 plays an important role in the regulation of cell proliferation, migration, and protein-protein interactions. Alteration of LASP-1 expression has been implicated in hepatocellular carcinoma. However, the functional involvement of LASP-1 in HCV propagation and HCV-induced pathogenesis has not been elucidated. Here, we first verified the protein interaction of NS5A and LASP-1 by both in vitro pulldown and coimmunoprecipitation assays. We further showed that NS5A and LASP-1 were colocalized in the cytoplasm of HCV infected cells. NS5A interacted with LASP-1 through the proline motif in domain I of NS5A and the tryptophan residue in the SH3 domain of LASP-1. Knockdown of LASP1 increased HCV replication in both HCV-infected cells and HCV subgenomic replicon cells. LASP-1 negatively regulated viral propagation and thereby overexpression of LASP-1 decreased HCV replication. Moreover, HCV propagation was decreased by wild-type LASP-1 but not by an NS5A binding-defective mutant of LASP-1. We further demonstrated that LASP-1 was involved in the replication stage of the HCV life cycle. Importantly, LASP-1 expression levels were increased in persistently infected cells with HCV. These data suggest that HCV modulates LASP-1 via NS5A in order to regulate virion levels and maintain a persistent infection.

• Molecules and Cells
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• 제27권3호
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• pp.329-336
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• 2009

To evaluate the involvement of translation initiation factors eIF4E and eIFiso4E in Chilli veinal mottle virus (ChiVMV) infection in pepper, we conducted a genetic analysis using a segregating population derived from a cross between Capsicum annuum 'Dempsey' containing an elF4E mutation ($pvr1^2$) and C. annuum 'Perennial' containing an elFiso4E mutation (pvr6). C. annuum 'Dempsey' was susceptible and C. annuum 'Perennial' was resistant to ChiVMV. All $F_1$ plants showed resistance, and $F_2$ individuals segregated in a resistant-susceptible ratio of 166:21, indicating that many resistance loci were involved. Seventy-five $F_2$ and 329 $F_3$ plants of 17 families were genotyped with $pvr1^2$ and pvr6 allele-specific markers, and the genotype data were compared with observed resistance to viral infection. All plants containing homozygous genotypes of both $pvr1^2$ and pvr6 were resistant to ChiVMV, demonstrating that simultaneous mutations in elF4E and eIFiso4E confer resistance to ChiVMV in pepper. Genotype analysis of $F_2$ plants revealed that all plants containing homozygous genotypes of both $pvr1^2$ and pvr6 showed resistance to ChiVMV. In protein-protein interaction experiments, ChiVMV viral genome-linked protein (VPg) interacted with both eIF4E and eIFiso4E. Silencing of elF4E and eIFiso4E in the VIGS experiment showed reduction in ChiVMV accumulation. These results demonstrated that ChiVMV can use both eIF4E and eIFiso4E for replication, making simultaneous mutations in eIF4E and eIFiso4E necessary to prevent ChiVMV infection in pepper.