• Journal of Yeungnam Medical Science
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• v.36 no.2
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• pp.67-77
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• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

• Journal of Life Science
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• v.32 no.12
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• pp.919-928
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• 2022

As seen in the COVID-19 pandemic, unexpected emergence of new viruses presents serious concern on public health. Especially, the absence of effective vaccines or antiviral drugs against emerging viruses significantly increases the severity of disease and duration of viral circulation among population. Natural products have served as a major source for safe and effective antiviral drugs. In this study, we examined the virucidal activity of medical herb extracts with a view to discover novel antiviral agents with desired levels of safety and antiviral efficacy. Ethanol extracts of ten selected medical herbs were tested for antioxidant activity and in-vitro cytotoxicity in various animal cell lines. Of note, the herbal extracts showed broad and potent virucidal activities against rotavirus, hepatitis A virus, and influenza A virus. The extracts of Sorbus commixta and Glycyrrhiza uralensis showed strong virucidal activities against influenza A virus. We also examined whether the extracts of Sorbus commixta and Glycyrrhiza uralensis can be used as inactivating agents to prepare an inactivated viral vaccine. In a mouse model, influenza A virus inactivated by the extracts elicited high levels of neutralizing antibodies, and the vaccination provided complete protection against lethal challenge. These results suggest that herb-derived natural products can be developed to antiviral drugs as well as inactivating agents for preparation of inactivated viral vaccines.

• Journal of Microbiology and Biotechnology
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• v.23 no.6
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• pp.771-778
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• 2013

Essential oils are increasingly of interest for use as novel drugs acting as antimicrobial and antiviral agents. In the present study, we report the in vitro antiviral activities of 29 essential oils, extracted from Chinese indigenous aromatic plants, against the tobacco mosaic virus (TMV). Of these essential oils, those oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass effected a more than 50% inhibition of TMV at 100 ${\mu}g/ml$. In addition, the mode of antiviral action of the active essential oils was also determined. Essential oils isolated from artemisia and lemongrass possessed potent inactivation and curative effects in vivo and had a directly passivating effect on TMV infection in a dose-dependent manner. However, all other active essential oils exhibited a moderate protective effect in vivo. The chemical constitutions of the essential oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass were identified by gas chromatography and gas chromatography-mass spectrometry. The major components of these essential oils were ${\alpha}$-zingiberene (35.21%), limonene (76.25%), terpinen-4-ol (41.20%), limonene (80.95%), 1,8-cineole (27.45%), and terpinolene (10.67%). The curative effects of 10 individual compounds from the active essential oils on TMV infection were also examined in vivo. The compounds from citronellal, limonene, 1,8-cineole, and ${\alpha}$-zingiberene effected a more than 40% inhibition rate for TMV infection, and the other compounds demonstrated moderate activities at 320 ${\mu}g/ml$ in vivo. There results indicate that the essential oils isolated from artemisia and lemongrass, and the individual compound citronellal, have the potential to be used as an effective alternative for the treatment of tobacco plants infected with TMV under greenhouse conditions.

• Journal of Microbiology and Biotechnology
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• v.26 no.11
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• pp.2012-2018
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• 2016

Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations ($100-10{\mu}g/ml$). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract ($100{\mu}g/ml$) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus.

• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.1-12
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• 2000

Although the first pyridazine was obtained in 1886, this heterocycle was not thoroughly investigated such isomers as pyrimidine and pyrazine especially in the field of drug development because pyridazine derivatives do not occur as natural products. Recently medicinal chemists have an growing interest in the pyridazine derivatives, since many Pyridazine derivatives were found to possess various potential therapeutic activities. In this paper sixty-eight pyridazine derivatives, which are already introduced as medicines or are being developed as drugs were classified according to their pharmacological activities, reviewed since 1955 and the relationship of structure-activities was discussed.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.561-571
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• 2016

Marine biosphere is the largest one of the earth and harbors an enormous number of different organisms. Living conditions differ fundamentally from those in terrestrial environment. The production of specific secondary metabolites is an important adaption mechanism of marine organisms to survive in the sea. These metabolites possess biological activities which make them interesting as possible drugs for human. The review presents sources, chemistry, production and pharmacology of FDA approved marine derived pharmaceuticals arranged according to their therapeutic indication. Four of the presently seven approved drugs are used for the treatment of cancer. Each another one is applicated for treatment of viral diseases, chronic pain and to lower triglyceride level in blood. Some other products are of interest in diagnostic and as experimental tools. Besides, this article describes challenges in drug development from marine sources, especially the supply problem.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5635-5641
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• 2015

Background: Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity. Materials and Methods: Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker. Results: Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK> Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product. Conclusions: Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.

• Health Policy and Management
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• v.28 no.4
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• pp.402-410
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• 2018

Background: Monitoring appropriate medication categories can provide early warning of certain disease outbreaks. This study aimed to present a methodology for selecting and monitoring medications relevant to the surveillance of acute respiratory tract infections, such as influenza. Methods: To estimate correlations between acute febrile respiratory tract infection and some medication categories, the cross-correlation coefficient (CCC) was used and established. Two databases were used: real-time prescription trend of antivirals, anti-inflammatory drugs, antibiotics using Drug Utilization Review Program between 2012 and 2015 and physicians' number of encounters with acute febrile respiratory tract infections such as influenza outbreaks using the national level health insurance claims data. The seasonality was also evaluated using the CCC. Results: After selecting six candidate diseases that require extensive monitoring, influenza with highly specific medical treatment according to the health insurance claims data and its medications were chosen as final candidates based on a data-driven approach. Antiviral medications and influenza were significantly correlated. Conclusion: An annual correlation was observed between influenza and antiviral medications, anti-inflammatory drugs. Suitable models should be established for syndromic surveillance of influenza.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.282-289
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• 2021

A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 µM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 µM). Peptide #2 inhibited the SARS-CoV-2 pseudovirus assay at IC50=1.49 µM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.552-558
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• 2016

Severe complications associated with EV71 infections are a common cause of neonatal death. Lack of effective therapeutic agents for these infections underlines the importance of research for the development of new antiviral compounds. In the present study, the anti-EV71 activity of norwogonin, oroxylin A, and mosloflavone from Scutellaria baicalensis Georgi was evaluated using a cytopathic effect (CPE) reduction method, which demonstrated that all three compounds possessed strong anti-EV71 activity and decreased the formation of visible CPEs. Norwogonin, oroxylin A, and mosloflavone also inhibited virus replication during the initial stage of virus infection, and they inhibited viral VP2 protein expression, thereby inhibiting viral capsid protein synthesis. However, ribavirin has a relatively weaker efficacy compared to the other drugs. Therefore, these findings provide important information that will aid in the utilization of norwogonin, oroxylin A, and mosloflavone for EV71 treatment.