• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.73-83
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• 1994

Applications of liposomes as a drug carrier for the oral delivery of poorly-absorbable macromolecular drugs have been limited, because of their instability in gastrointestinal environments including pH, bile salts, and digestive enzymes. Two polysaccharides, dextran(DX) and pullulan(PL), were introduced to the preformed liposomes in order to enhance the stability. Palmitoyl derivatives of polysaccharides, palmitoyldextran(PalDX) and palmitoylpullulan(PalPL), were synthesizd and introduced to the liposomes during preparation for the same purpose of stability. The effects of these polysaccharides coating were evaluated basically by physical properties of particle size distribution and optical microscopy, then compared with uncoated liposomes by the observations of both in vitro stability and in vovo absorption characteristics. The geometric mean diameters of polysaccharide-coated liposomes were greater than that of uncoated liposome, showing the outermost polysaccharide-coated layer under the optical microscopy. In vitro stabilities of uncoated or polysaccharides-coated liposomes were measured by turbidity changes in various pH buffer solutions containing sodium choleate as bile salts. While uncoated liposome was very sensitive to bile salts, polysaccharides-coated liposomes were stable in relatively higher concentrations of sodium choleate, giving the results of better stability of PalDX- and PalPL-coated liposomes than that of DX- and PL-coated liposomes. After liposomal encapsulation of acyclovir(ACV), an antiviral agent as a model drug, it has been administered orally to rats as dose of ACV 40 mg/kg. Plasma concentrations of ACV were assayed by HPLC and analyzed by model-independent pharmacokinetics. Pharmacokinetic parameters of Cmax, tmax, and [AUC] have been compared.

• Molecules and Cells
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• v.44 no.9
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• pp.688-695
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• 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.

• Korean Journal of Clinical Pharmacy
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• v.29 no.1
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• pp.56-60
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• 2019

Oseltamivir is an antiviral medication prescribed to prevent and treat influenza A and B. A case from a community pharmacy in Korea was reported for an adverse event associated with oseltamivir administration. A 20-month-old boy had psychiatric symptoms after receiving 2 doses of oseltamivir. Therefore, an evaluation of whether the psychiatric symptoms were caused by oseltamivir was required. To determine whether the adverse event resulted from the administrated medication or other factors, three tools were used: the Naranjo scale, the Korean causality assessment algorithm (Ver.2), and the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria. The psychiatric symptoms occurred after oseltamivir administration, and were attenuated after oseltamivir termination. A possible cause of the psychiatric symptoms is high fever, but information on the body temperature of the patient was not sufficient. Therefore, it was unclear whether there were other nonpharmacological causes of adverse drug reaction. For these reasons, in terms of causality, the results evaluated by the three tools represented, "possible", "probable", and "probable/likely", respectively.

• Journal of Life Science
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• v.34 no.6
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• pp.408-417
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• 2024

It was confirmed whether PB-81, a 50% ethanol extract of Daphne genkwa (Siebold & Zucc), had an inhibitory effect on virus proliferation in bovine rotavirus and a therapeutic effect on bovine diarrhea disease. The results showed that PB-81 induced the interferon beta in A549 cells, an epithelial cell line and interferon gamma in NK92 cells, a blood cell line. Furthermore, to confirm the viral proliferation inhibitory effect of PB-81, PB-81 was administered to MBDK cell line before, during, and after infection. Result shows that the virus was suppressed in all cases where PB-81 was administered, and the best virus suppression effect was achieved when PB-81 was administered before virus infection. In the toxicity test in mice, no side effects due to toxicity were observed, even at a maximum dose of 20 mg/mL. To verify the therapeutic effect on 16 cattle with bovine rotavirus diarrhea and 4 cattle in the control group, PB-81 was administered at a dose of 20 mg/5 mL, and No fatality was observed during the treatment. The average recovery duration from the initial administration of PB-81 was 2.25 days in the PB-81 administration group and 6.5 days in the control group without PB-81 administration. No side effects were observed from the tested cattle with rotavirus diarrhea.

• The Korean Journal of Mycology
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• v.27 no.3 s.90
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• pp.237-241
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• 1999

To search for less toxic antiviral agents from Basidiomycetes, the water soluble components (=EA), were isolated from the carpophores of Elfvingia applanata (Pers.) Karst. Anti-varicella zoster virus (Oka strain; anti-VZV/Oka) activity of EA was examined in MRC-5 cells by plaque reduction assay in vitro. And the combined antiviral effects of EA with interferon (IFN) alpha or IFN gamma were examined on the multiplication of VZV/Oka. EA exhibited a dose-dependent reduction in the plaque formation of VZV/Oka with 50% effective concentration $(EC_{50})$ of $464.14\;{\mu}g/ml$. The results of the combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combination of EA with IFN alpha showed partially synergistic or additive effects with CI values of $0.83{\sim}1.09$ for 50%, 70%, 90% effective levels, and those with IFN gamma showed antagonism with CI values of $1.20{\sim}1.24$.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.176-176
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• 1994

Moraceae comprise a large family of sixty genera and neary 1,400 specieses, including important groups such as Artocarpus, Morus, and Ficus. In particular, Morus(mulberry) is a small genus of tree and shrubs found in temperate and subtropical regions of the Northern hemishere and has been widely cultivated in China and Korea, In addition, the root bark of mulberry tree have been used as an antiphlogic, diuretic, and expectorant in white medicine, and the crude drug is known as "Sangbaikpi" in Korea. Recently, some papers have been published reporting the hypotensive effect, antiviral effect, antifungal effect, inhibitory effect of cAMP-phosphodiesterase, and anticancer effect of this extract. Little is known about that Cortex mori could have been an antiallergic effect. The purpose of this study was the development of an antiallergic agent with an antiallergic effect from Cortex mori. For this, several in vivo and in vitro experimental models were used. Results are 1) Cortex mori inhibited the compound 48/80-induced degranu-lation, histamine release and calcium uptake of rat peritoneal mast cells, 2) compound 48/80-induced anaphylactic shock and cutaneous reaction were significantly inhibited by pretreatment of Cortex mori, and 3) Cortex mori inhibited the ovalbumin-induced late astmatic reaction. From the above results it is suggested that Cortex mori has some substances with an antiallergic activity. Our final purpose of this study is to develope the new drug with an antiallergic activity from Cortex mori

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.311-319
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• 2020

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC₅₀ values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.169-176
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• 2004

Acyclovir(ACV) is an important antiviral drug used extensively against infections caused by herpes viruses, especially herpes simplex and varicella zoster. Because of high crystallinity and large particle size, solubility of intact ACV is very low in water(1.3 mg/ml). The goal of this work is to enhance the solubility of ACV. To make solid dispersion, Polyethyleneglycol, Hydroxyprophylmethylcelluose and Polyvinylpyrrolidone were used as polymer carriers in this work. Polymer carriers and drug were dissolved in acetic acid. And then spray drying method and freeze drying method were used as solvent extraction. Morphology, crystallization and functional group were characterized using SEM, XRD and FT-IR. The result of in vitro test showed the sample using PVP as polymer carrier had higher dissolution rate(up to 466%) than intact ACV.

• The Korean Journal of Food & Health Convergence
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• v.6 no.4
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• pp.17-19
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• 2020

HIV/AIDS disease still remain a global pandemic and it's management has undergone series of treatment changes and improvement although there is still no permanent cure.Dolutegravir belongs to a group of HIV drugs called integrase inhibitors. Integrase inhibitors block an HIV enzyme called integrase. By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.Dolutegravir combination based regimen has turned out to be very effective (antiviral) with negligible rare side effects on clients. This drug (Dolutegravir based regimen) combination has successfully increased the appetite for food of all the clients, unlike others and has shown to reduce viral load in the most shortest period ever. It can be deduced that development of resistant mutant virus will be reduced if not eliminated with dolutogravir based regimen.The role of Continuous adherence counseling has shown to improve clients treatment management. It is important to note that the availability of food has direct effect on the economic status or financial weight on the client. Hence the progress that is increase in body mass index (BMI) is a direct impact of the availability of food for the clients.

• Genomics & Informatics
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• v.20 no.3
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• pp.33.1-33.17
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• 2022

Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of -9.7, -9.5, -9.1, and -9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.