• Korean Journal of Microbiology
• /
• v.29 no.1
• /
• pp.25-33
• /
• 1991

Antiviral activities of papaverine and nucleoside analogs, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and acyclovir, against human cytomegalovirus (HCMV) infection were compared in vitro. Papaverine and DHPG were effective in reducing infectious HCMV yields with $ED_{50}{\s}$ (effective dose 50: the concentraion at which 50% of virus yields was obtained) of approximately 1.02 and $0.45{\mu}{\M}$, respectively; while acyclovir was less effective with an $ED_{50}$ of about $10.4{\mu}{\M}$The relative cytotoxicity of these drugs was evaluated under the same conditions used to measure infectious HCMV yields. Papaverine and DHPG demonstrated little cellular toxicity as measured by their effect on the viability of confluent cells at concentrations in the range of those demonstrating potent inhibition of HCMV replication. Similarly, protein synthesis was largely unaffected by these drugs in stationary mock-infected cells as measured by the incorporation of isotopically labelled amino acids. In contrast, cellular DNA synthesis was invariably reduced in the presence of either drug. HCMV-specific DNA synthesis was also strongly inhibited by papaverine and DHPG.

• Korean Journal of Pharmacognosy
• /
• v.49 no.4
• /
• pp.291-297
• /
• 2018

Coxsackievirus B3 (CVB3) is a very well-known causative agent for viral myocarditis and meningitis in human. However, the effective vaccine and therapeutic drug are not developed yet. CVB3 infection activates host cell AKT signaling. Inhibition of AKT signaling pathway may attenuate CVB3 replication and prevent CVB3-mediate viral myocarditis. In this study, we determined antiviral effect of the selected natural plant extract to develop a therapeutic drug for CVB3 treatment. We screened several chemically extracted natural compounds by using HeLa cell-based cell survival assay. Among them, Linum usitatissimum L. extract was selected for antiviral drug candidate. L. usitatissimum extract significantly decreased CVB3 replication and cell death in CVB3 infected HeLa cells with no cytotoxicity. CVB3 protease 2A induced eIF4G1 cleavage and viral capsid protein VP1 production were dramatically decreased by L. usitatissimum extract treatment. In addition, virus positive and negative strand genome amplification were significantly decreased by 1 mg/ml L. usitatissimum extract treatment. Especially, L. usitatissimum extract was associated with inhibition of AKT signal and maintain mTOR activity. In contrast, Atg12 and LC3 expression were not changed by L. usitatissimum extract treatment. In this study, the potential AKT signal inhibitor, L. usitatissimum extract, was significantly inhibited viral genome replication and protein production by inhibition of AKT signal. These results suggested that L. usitatissimum extract is a novel therapeutic agent for treatment of CVB3-mediated diseases.

• The Korean Journal of Mycology
• /
• v.27 no.2 s.89
• /
• pp.175-179
• /
• 1999

In order to find less toxic antiviral agents from Basidiomycetes, EA, the water soluble substance, was prepared from the carpophores of Elfvingia applanata (Pers.) Karst. Antiviral activity of EA against vesicular stomatitis virus [New Jersey serotype, VSV(NJ)] was examined in Vero cells using plaque reduction assay in vitro. And the combined antiviral effects of EA with interferon (IFN) alpha and gamma were examined on the multiplication of VSV(NJ). EA caused a concentration-dependent reduction in the plaque formation of VSV(NJ) with 50% effective concentration $(EC_{50})$ of 2.10 mg/ml. The results of combination assay were evaluated by the combination index (CI) that was analysed by the multiple drug effect analysis. The combination of EA with IFN alpha showed more potent effect with CI values of $0.87{\sim}1.59$ for 50%, 70% and 90% effective levels than that with INF gamma with CI values of $1.05{\sim}2.03$.

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

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

• Journal of the Korea Institute of Military Science and Technology
• /
• v.27 no.1
• /
• pp.107-115
• /
• 2024

Various vaccines were rapidly developed during the COVID-19 pandemic to prevent and treat infections but global infections continue, and concerns about new mutations and infectious diseases persist. Thus, active research focuses on developing, producing, and supplying vaccines and treatments for various infectious diseases and potential pandemics. Natural killer(NK) cells, as innate immune cells, can recognize and eliminate abnormal cells like virus-infected and cancer cells. Hence, their development as anticancer and antiviral treatments is rapidly advancing. In this study, optimal short-term culture conditions were identified for allogeneic NK cells by simplifying the culture process through the isolation of NK cells(referred to as NKi cells) and eliminating CD3+ cells(referred to as CD3- cells). NK cells demonstrated reduced viral titer in injection of NK cells into SARS-CoV-2 infected ACE-tg mice increased survival. The study's findings could form the basis for an antiviral treatment platform that swiftly responds to new viral disease pandemics.

• YAKHAK HOEJI
• /
• v.56 no.3
• /
• pp.204-209
• /
• 2012

The purpose of this study was to construct database for a drug safety information website to serve as an access point of up-to-date resources for a wide variety of drug-safety information helping patients and healthcare professionals make well-informed decisions about medication use. All the contents developed were confirmed by the council of advisors who were the experts in drug safety. The detailed contents of database on frequently prescribed drug including 9 NSAIDs, 19 antibiotics, 24 cardiovascular, 21 metabolic, 14 respiratory, 20 digestive, 22 hormonal, 10 genitourinary, 10 anti-allergic, 27 antifungal/antiviral, and 71 neuropsychiatric agents were developed based on the approved drug labeling of the Korean FDA. A separately searchable database of drug-specific safety information for patients and health professionals was constructed for users in need of different depth of knowledge on using medications safely. The safety information on highly prevalent chronic diseases and drug classes was also developed. Finally the most recent global drug safety news was provided. The consumer directed information was developed in layman's terms as means of proving user-friendly information. The creation of this type of website is part of the Korean FDA's ongoing initiative to address and promote the safe use of medications for the public.

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

• Journal of Marine Bioscience and Biotechnology
• /
• v.1 no.3
• /
• pp.144-155
• /
• 2006

This report reviews the literatures on chemical constituents of marine sponges of the genus Spongosorites and also highlights our own research. Specific biological activities of the metabolites from these sponges include: cytotoxic, antitumor, antibacterial, antifungal, antiviral, anti-inflammatory, and other pharmacological activities.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.4
• /
• pp.1293-1297
• /
• 2011

To improve the biological activities of rupestonic acid, 21 new rupestonic acid fatty ester derivatives (2a-2h) and aromatic ester derivatives (2i-2u) were synthesized and preliminarily evaluated for their anti-influenza activity in vitro by the national center for drug screening of China, using the Oseltamivir and Ribavirin as reference drugs. The results showed that 2l ($IC_{50}=0.5{\mu}mol/L$) exhibited potent anti-influenza $A_3$ viral activity among the synthesized compounds and was 10-fold more potent than that of the reference drug Oseltamivir ($IC_{50}=5.1{\mu}mol/L$).