• BMB Reports
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• v.53 no.3
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• pp.166-171
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• 2020

A chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent viruslike particle (trVLP) system implementing the whole Ebola virus (EBOV) life cycle. Dose-dependent inhibition of Ebola trVLP replication was induced by 15 hit compounds, which primarily target different types of G protein-coupled receptors (GPCRs). Based on the chemical structure, the compounds were divided into three groups, diphenylmethane derivatives, promazine derivatives and chemicals with no conserved skeletons. The third group included sertindole, raloxifene, and ibutamoren showing prominent antiviral effects in cells. They downregulated the expression of viral proteins, including the VP40 matrix protein and the envelope glycoprotein. They also reduced the amount of EBOV-derived tetracistronic minigenome RNA incorporated into progeny trVLPs in the culture supernatant. Particularly, ibutamoren, which is a known agonist of growth hormone secretagogue receptor (GHSR), showed the most promising antiviral activity with a 50% effective concentration of 0.2 μM, a 50% cytotoxic concentration of 42.4 μM, and a selectivity index of 222.8. Here, we suggest a strategy for development of anti-EBOV therapeutics by adopting GHSR agonists as hit compounds.

• Bulletin of the Korean Chemical Society
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• v.27 no.7
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• pp.976-980
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• 2006

The synthesis of 4'-phenyl and 1'-methyl doubly branched carbocyclic nucleoside was accomplished from 2-hydroxy acetophenone. The 4'-phenyl group was installed via a [3,3]-sigmatropic rearrangement reaction, and the carbonyl addition of methylmagnesium bromide was used to introduce the 1'-methyl group. Cyclization of divinyl 9 was performed using $2^{nd}$ generation Grubbs catalyst. The coupling of cyclopentenol 12$\alpha$ with 6-chloropurine by Mitsunobu reaction and desilylation was used to synthesize the target nucleoside 15.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.65.1-65.1
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• 2003

Natural benzo[c]phenanthridine and protoberberine alkaloids which have been attractive to synthetic organic chemists and biochemists over the last 2 decades since such compounds have shown interesting biological properties such as antitumor, antiviral and antimicrobacterial activities. For the systematic research on these alkaloids, several total syntheses of these alkaloids have been reported. However, the bulk of reported benzo[c]phenanthridine synthetic studies to date have involved multistep sequences for assembly of the target molecules as well as lack of generality for synthesizing substituted molecules. (omitted)

• Journal of Microbiology and Biotechnology
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• v.26 no.1
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• pp.151-159
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• 2016

Nanoparticles have wide-scale applications in various areas, including medicine, chemistry, electronics, and energy generation. Several physical, biological, and chemical methods have been used for synthesis of silver nanoparticles. Green synthesis of silver nanoparticles using plants provide advantages over other methods as it is easy, efficient, and eco-friendly. Nanoparticles have been extensively studied as potential antimicrobials to target pathogenic and multidrug-resistant microorganisms. Their applications recently extended to development of antivirals to inhibit viral infections. In this study, we synthesized silver nanoparticles using Cinnamomum cassia (Cinnamon) and evaluated their activity against highly pathogenic avian influenza virus subtype H7N3. The synthesized nanoparticles were characterized using UVVis absorption spectroscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy. Cinnamon bark extract and its nanoparticles were tested against H7N3 influenza A virus in Vero cells and the viability of cells was determined by tetrazolium dye (MTT) assay. The silver nanoparticles derived from Cinnamon extract enhanced the antiviral activity and were found to be effective in both treatments, when incubated with the virus prior to infection and introduced to cells after infection. In order to establish the safety profile, Cinnamon and its corresponding nanoparticles were tested for their cytotoxic effects in Vero cells. The tested concentrations of extract and nanoparticles (up to 500 μg/ml) were found non-toxic to Vero cells. The biosynthesized nanoparticles may, hence, be a promising approach to provide treatment against influenza virus infections.

• The Journal of Dong Guk Oriental Medicine
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• v.1
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• pp.209-236
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• 1992

The microculture XTT antiviral assay method is used to quantitate HIV-1 induced cytopathic effects as modulated by test substances. This relatively simple assay facilitated the safe and rapid determination of in vitro antiviral activity of selected chemicals as well as direct cytotoxicity. This experiment also confirmed that this system measures infection and subsequent viral replication in target cells and XTT formazan formations correlated with the accumulation of extracellular virions, as measured by quantitative HIV-1 induced syncytium foramtion. The present results with Glycyrrhizin using this in vitro culture system demonstrated that effective dose, EC50(the concentration at which increases XTT formazan production in infected cultures to 50% of that in untreated, uninfected controls) was 250ml. As comparison, AZT was included in this experiment and demonstrated that EC50 AZT of was 0.05g/ml, approximately 5,000 times more potent than Glycyrrhizin based on EC50 ratio's alone. However, this potency is limited by severe cytotoxicity of AZT, while Glycyrrhizin is approximately 16 times less toxic(IC50 of Glycyrrhizin 800 and AZT 51 g/ml). While AZT's anti-HIV-1 viral activity is mediated by inhibition of reverse transcriptase of the virus, Glycyrrhizin faild to demonstrate any inhibitory activity against reverse transcriptase. Further study is necessary in order to understand the precise mechanisms of Glycyrrhizin action against HIV-1 viruses. Althouth Glycyrrhizin is less effective antiviral agent than AZT, much less toxicity of Glycyrrhizin is desirable in terms of chronic treatment. Combination treatment of AZT and Glycyrrhizin may be therapeutically beneficial. Clinical effectiveness of two drug combination therapy for AIDS patient is unknown at this time. However, this experimental investigation presents the scientific rational basis for such therapeutic approach.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.425-431
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• 1997

To examine components of Ganoderma lucidum for anti-human immunodeficiency virus (HIV) activity, the aqueous extracts of its basidiocarps were separated into high-molecular-weight (HMF) and low-molecular-weight (LMF) fractions. These fractions were used in XTT [2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide] antiviral assay which can quantitatively measure cytopathic effects of HIV-1 on CEM, human T lymphoblastoid cell line. The CEM cell line added with serial diluted HMF or LMF was cultured in the absence or presence of HIV-1. The results showed that the LMF of the aqueous extract strongly inhibited cytopathic effect of the target cell induced by HIV-1. When two-fold serially diluted LMF ranging from $40.97{\mu}g/ml$4 to 125.00 .mu.g/ml was added to the virus-free culture system, no toxicity on the target cells was detected in all the concentrations tested. However, when it was added to the HIV-infected culture system, the viabilities of the target cell reached a plateau recovering its viabilities to 71.7% and 82.5% in experiment-1 and -2 at 15.60 .mu.g/ml, respectively. The cell viabilities were then gradually decreased but maintained at more than 50% above 31.20 .mu.g/ml concentration. On the contrary, HMF did not prevent any HIV-induced cytopathic effect at any concentrations tested on this cell line. From these results, negligible toxicities were observed by both HMF and LMF of G. luciolum, and recovery of cell viability in HIV infected target cell was induced only by LMF of the carpophores.

• International Journal of Industrial Entomology and Biomaterials
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• v.13 no.1
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• pp.31-35
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• 2006

The ubiquitin conjugating enzyme 2 (E2) is core component of ubiquitin proteasome pathway (UPP) which represents a selective mechanism for intracellular proteolysis in eukaryotic cells. The E2 has been implicated in the intracellular transfer of ubiquitin to target protein. We show here the involvement of E2 in antiviral immune of Bombyx mori to Bombyx mori nuclear polyhedrosis virus (BmNPV). In this study, mRNA fluorescent differential display PCR (FDD-PCR) was performed with BmNPV highly resistant silkworm strain NB and susceptible silkworm strain 306. At 24 h post BmNPV infection, FDD-PCR with the arbitrary primer AP34 showed that one cDNA band was down-regulated in the midgut of resistant strain, but highly expressed in susceptible strain. The deduced amino acid sequence of this cDNA clone share 99% identity with the recently published B. mori ubiquitin conjugating enzyme E2 (Genbank NO: DQ311351). Fluorescent quantitative PCR corroborated down regulation of E2 in resistant strain. We there conclude that BmNPV infection evokes strong response of susceptible strain including activation of UPP. BmNPV may evolve escape mechanisms that manipulate the UPP in order to persist in the infected host. In addition, the identification of down-regulation of E2 in resistant strain, as well as structure data, are essential to understanding how UPP operates in silkworm antiviral immune to BmNPV disease.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.353.3-354
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• 2002

The reverse transriptase (RT) of HIV-1 is a proven target for inhibition of HIV-1 replication. Many nonnucleoside RT inhibitors (NNRTls) are in development stage for the clinical use: Among them. trovirdine (PETT). (thiophene) ethylpyridylthioureas (TET). and phenylethylpyridylureas (urea-PETT) are simple and flexible arylalkylarylureas. These are now considered to be very important as a potential therapeutics with remarkable antiviral activity against various mutant strains. (omitted)

• Journal of Integrative Natural Science
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• v.6 no.3
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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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.365.2-365.2
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• 2002

S-Adenosylhomocysteine hydrolase (SAH) catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L -homocysteine and has been an attractive target for the development of broad spectrum antiviral agents. Neplanocin A and 9-(dihydroxycyclopent-4' -enyl)adenine (DHCeA) have been known to inhibit SAH by cofactor (NAD＋) depletion mechanism and their inhibition is reversed by the addition of NAD＋ or dialysis. (omitted)