• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.116-121
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• 2004

To observe the intervening effect of resveratrol on coxsackie virus B3m-induced myocarditis in Balb/c mice and explore the mechanism of intervening effect. Using an animal model of viral myocarditis induced by coxsackie virus B3m (CVB3m), with Ribavirin and Astragalan as comparison, to examine the changes of general condition, mortality, the weights of heart, liver and spleen, serum MDA and NO levels, and cardiac histology in Balb/c mice. By comparison with Ribavirin and Astragalan, it was found that in the mice model of viral myocarditis induced by coxsackie virus B3m resveratrol significantly improved the changes of general condition, mortality, the weights of heart, liver and spleen, serum MDA and NO levels, and cardiac histology. It suggested that resveratrol may have some chemopreventive and chemotherapeutic effects in the treatment of viral myocarditis.

• The Journal of Korean Society of Virology
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• v.26 no.2
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• pp.215-225
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• 1996

Aseptic meningits, an acute inflammation of the meninges, is a common illness during childhood. Virus is the most important cause of aseptic meningitis. Especially enterovirus causes approximately above 85% of all cases of aseptic meningitis. In 1993, there was a big epidemic of aseptic meningitis by ECHO 9 and ECHO 30 viruses. And ECHO 3 virus was isolated as a causative agent of aseptic meningitis in 1994. This study was aimed to detect the causative agent of aseptic meningitis in 1995 and to analyze the 5'-noncoding region which was used to detect virus. Virus was isolated from 87 stools and cerebrospinal fluid specimens of the patients by cultured RD and HEp-2 cell. Neutralizing antibody tests using enterovirus serum pool were performed on the specimens with cytopathic effect. 3 of ECHO 7 viruses and 5 of Coxsackie B3 viruses were isolated from stool specimens and 1 of ECHO 7 and Coxsackie B3 mixed type was confirmed from cerebrospinal fluid specimens. RNA was isolated from the culture supernatants of infected cells and general primers were selected in highly conserved part of the 5'-noncoding region of the enteroviral genome for RT-PCR. PCR product from this virus showed a 152bp band on gel electrophoresis. Sequence of obtained DNA was compared with prototype sequences by accessing to the Genebank database. 5'-noncoding region of isolated Coxsackie B3 virus, which has point mutations in nucleotide sequence positions 493, 497, 502, 523, was closely related to that of polio virus type 1, Mahoney strain. In case of isolated ECHO 7 virus, nucleotide has been changed from cytosine to thymine at position 581 and from thymine to cytosine at position 583. We concluded the causative agents of the outbreak of aseptic meningitis during June to July in 1995 were both ECHO 7 and Coxsackie B3 virus, and the primer used in this study could allow a rapid diagnosis of enteroviruses by PCR.

• Pediatric Infection and Vaccine
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• v.6 no.1
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• pp.123-130
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• 1999

Purpose : Meningitis is an inflammation of meninges by various kinds of organisms. Almost 85% of aseptic meningitis is caused by Enterovirus. This study was done to detect the causative virus of those with aseptic meningitis through sequencing the 5'-noncoding region to compare prototype and homology. Methods : RNA was extracted from Coxsackie Bl, Echovirus 3, 7, 9, 30. DNA was synthesized by RT-PCR and we compared homology with prototype from WHO by direct sequencing. Results : 1) PCR products from these viruses showed same bands of 155 bp and 440 bp on gel electrophoresis. 2) Coxsackievirus and Echovirus 11 prototype sequences were compared, which showed 12 bp changes with 92.1%. 3) Coxsackievirus B1 from a patient showed 94.1% homology when compared with prototype. 4) Echovirus 3 showed 92.8%, echovirus 7 92.8%, echovirus 30 82.9% homology. Conclusion : 5'-NCR of enterovirus has high homology which was good for use of diagnosis and more long sequencing requires for typing of viruses.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2297-2304
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• 2013

A series of novel benzimidazole derivatives bearing a heterocyclic ring as oxadiazole (21-32), thiadiazole (33-34), triazole (35-36) were synthesized and evaluated for their activities against Coxsackie virus B3 and B6 in Vero cells. Compounds 21-26, 31-36 with moieties of 2'-pyridyl, 3'-pyridyl and 4'-pyridyl at the 2-position and oxadiazoles, thiadiazole, or triazole substituent at the 4- or 5-position generally displayed activities against CVB3 and CVB6. Especially compound 24 ($IC_{50}=1.08{\mu}g/mL$, SI = 61.7 against CVB3) was the promising candidate as lead compound for anti-enteroviral drug. It was observed in the incorporation of heterocyclic rings in benzimidazole at the 5-position could enhance their biological activities.

• Proceedings of the Korean Society of Life Science Conference
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• 2000.12a
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• pp.20-26
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• 2000

호흡기계 및 소화기계에 감염된 전염성 바이러스에 대한 역학적 기초자료로 이용하고자 1999년 1월부터 12월까지 부산지역에서 분리된 전염성 바이러스의 특징과 계절적 발생추이, 환자의 성별, 연령별 발생에 대해 조사한 결과는 다음과 같다. 1. 1999년도 바이러스 가검물 2261건에서 분리한 호흡기계감염 바이러스 279건과 소화기계 감염 바이러스 83주를 분리하였으며, 이중 인플루엔자 바이러스 A형이 96주(29.6%), B형이 107주(33.0%)로 대부분을 차지하였다. 2. 1999년의 바이러스 분리의 성별 분포는 총 360명의 환자 중 179명(49.7%)의 남성 및 181명(50.3%)의 여성으로 비슷한 양상을 나타내었다. 이중 호흡기계의 경우 279명의 감염환자 중 남성이 130명(46.6%), 여성이 149명(53.4%)으로 여성의 감염율이 비교적 높았으나, 소화기계의 경우 83명의 감염환자 중 남성이 51명(61.4%), 여성이 32명(38.5%)으로 남성의 감염율이 거의 2배정도 높게 나타났다. 3. 1999년의 연령별 분포는 10세 이하의 어린이가 194명(59.9%)으로 대부분을 차지하였으며, 이중 인플루엔자 바이러스가 99명(30.6%)으로 가장 높은 감염을을 나타내었다 유행성이하선염 바이러스의 감염어린이 중에 $l1{\sim}15$세의 연령층이 15명으로(53.3%)로 가장 높게 나타났다. 4. 1999년 월별 감염율은 호흡기계 감염증 바이러스의 경우 1월부터 4월까지, 그리고 12월에 증가 추세를 보이면서 4월에 가장 높은 감염율을 나타내었다 소화기계 감염증 바이러스의 경우 9, 10, 11월을 제외한 모든 월별에 관찰되었으며, echo와 coxsackie 바이러스는 무균성 수막염 환자에서 하절기에 집중적으로 발생하였다. 동절기에 유행하는 설사 바이러스는 12월에 비교적 높은 양상을 나타내었다. 5. 인플루엔자 바이러스는 MDCK 세포에서, 아데노 바이러스와 유행성 이하선염 바이러스는 HEp-2 세포에서, 파라인플루엔자 바이러스는 Vero 세포에서, 그리고 echo, coxsackie B 바이러스와 장내 바이러스는 HEp-2, Vero, BGM 세포에서 뚜렷한 세포병변 효과를 나타내었다. 6. 분리한 바이러스는 전자현미경으로 관찰한 결과 인플루엔자 바이러스 A 형(HINI, H3N2)은 95nm, B 형은 70nm크기의 구형을 나타내었으며, 바이러스표면의 지질 이중층이 뚜렷하게 관찰되었다. 아데노 바이러스는 외피가 관찰되지 않았으며, nucleocapsid는 symmetry이고 크기는 71nm로서 바이러스 입자 표면에 icosaheral capsomer의 배열이 명확하게 관찰되었고, 파라인플루엔자 바이러스와 유행성 이하선염 바이러스는 외피가 있는 구형의 큰 viron으로180, 170nm 크기이었다. 7. Echo와 coxsackie B group 바이러스는 모두 외피가 없는 isometric 형으로 크기는 $30{\sim}45nm$ 이었고, enteric adeno 바이러스는 84nm 크기로서 외피가 없고, 입자 표면에 capsomer의 배열이 명확하게 관찰되었고, rotavirus는 크기가 70nm이며 외층 capsid 단백질과 내층 capsid 단백질이 두층으로 되어 있는 전형적인 수레바퀴 모양을 나타내었다. 이상의 결과로 보아 호흡기계 및 소화기계에 감염되는 전염성 바이러스는 연중 지속적으로 분리되고 있으며 전염성이 강하여 집단 발생은 일으키는 경우도 많고 최근 들어 유행성 이하선염과 흥역 바이러스의 발생률이 높은 추이를 나타내고 있지만 아직은 특이한 바이러스 치료제가 개발되어 있지 않았으므로 지속적인 대책과 아울러 장기적인 발생 가능에 대한 예방책을 흥보하여야 할 것으로 보이며 계속적인 바이러스성 전염병 유행예측조사 및 역학조사가 적극적으로 이루어져야 할 것으로 사료된다.

• YAKHAK HOEJI
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• v.56 no.4
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• pp.230-235
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• 2012

Synthesis of novel cyclopropyl pyrimidine and purine nucleoside derivatives 2~8 with ${\alpha}$-configuration was successfully accomplished using an epoxide-ring opening reaction, lactonization, a hydroboration-oxidation reaction and a Mitsunobu reaction as the key steps. Antiviral activities against HSV-1 and -2, HIV-1 and -2, coxsackie B1and B3 viruses and poliovirus were assayed. Three compounds 4, 7 and 8 exhibit cytotoxicity-derived antiviral activity only in HIV-1 and -2.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.112-112
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• 1993

바이러스 치료제 개발을 위하여 합성된 핵산유도체 11개에 대한 in vitro 항바이러스 약효검색을 수행하였다. 검색대상 바이러스로서 외피보유 DNA 바이러스인 human herpesvirus에 속하는 herpes simplex virus type 1과 type 2에 대해서는 Vero 세포체계에서 3일 후 CPE 저해정도를 MTT 검색법으로 cytomegalovirus에 대해서는 HEL 세포체계에서 7일 후 Giemsa 염색법으로 약효를 측정하였다. 외피비보유 RNA 바이러스인 picornavirus에 속하는 poliovirus type 1과 type 3과 coxsackie B virus type 3에 대한 약효를 HeLa 세포체계에서 2일 후 CPE 저해정도를 MTT 검색법으로 측정하였다. 아울러 selectivity index를 구하기 위하여 Vero와 HeLa 세포에 대한 약물자체의 독성인 cytocidal effect를 MIT 검색법으로 측정하였다. 그 결과 항 herpesvirus 약효는 어떤 물질에서도 발견되지 않았으나 한 물질이 poliovirus type 1과 3에 대하여 selectivity index 10정도 (CC$_{60}$ 38 ug/ml, EC$_{50}$ 1-4 ug/ml)를 나타내었고 자세한 기작은 좀 더 조사할 필요가 있다.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.315-323
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• 2000

Syntheses of new analogues of oxathiin carboxanilide (UC84) and their antiviral activities were described. The heterocyclic carboxylic acids including oxathiins (4), thiazines (9) and dithiins (13) in which the methyl was replaced either by lipophilic trifluoromethyl- or bulky phenylgroup were synthesized starting from $\beta$-keto esters (5). Reaction of 4, 9 and 13 with thionyl chloride followed by treatment of the substituted aniline 22 gave the corresponding carboxanilides (24a~24f). The carboxanilides were subjected to Laweson's reagent the corresponding thiocarboxanilides (24g~24k). The antiviral activities of the synthesized compounds against human immunodeficiency virus type 1 (HIV-1), poliovirus type 1 (PV-1 ), coxsackie B virus type 3 (CoxB-3), vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) were presented. The antiviral activity against HIV-1 of dithiin carboxanilide (24e) was similar with that of UC84 (24a). The corresponding thiocarboxanilides (24g~24k) showed higher inhibitory activity against HIV-1 than the carboxanilides (24a, 24b, 24d, 24e). The compounds in which ether the lipophilic trifluorormethyl substituents (24d, 24f, 24i ,24k) or bulky phenyl substituent is present in the heterocyclic compounds showed lower inhibitory activity than that of the methyl substituents is present in the compounds against the HIV-1. But the trifluoromethylated dithiin (24f) showed higher inhibitory activity against PV-1 and CoxB-3 virus than commercial antiviral agents, ribavirin (RV).

• Pediatric Infection and Vaccine
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• v.14 no.1
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• pp.47-54
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• 2007

Purpose : Viral respiratory tract infection is most common cause for admission to hospital in children. There are many cases with elevated transaminase level in patients with viral lower respiratory tract infection (LRTI). The aim of this study was to compare indexes of disease severity such as duration of assisted ventilation, length of hospital stay and Respiratory Distress Assessment Instrument (RDAI) score in children with viral LRTI with and without elevated transaminase levels and to determine the etiology related to elevated transaminase levels in this patients group. Methods : Virological analysis was done from respiratory specimens obtained from patients with LRTI admitted to Kangnam Sacred Heart Hospital from Jan. 2003 to Jun. 2005. Viral diagnosis was made by isolation of viruses employing HEp-2 cell culture from nasopharyngeal aspiration. Medical records of children were reviewed retrospectively. We compared age, sex, RDAI score, Respiratory Rate (RR) score and mean duration of hospital stay between patients with elevated transaminase levels (Patient Group) and patients with normal transaminase levels (Control Group). Results : Viruses were isolated from 181 children with LRTI. 16 cases were excluded according to criteria. 28 cases (17.0%) had elevated transaminase levels (Patient group) and 137 cases (83.0%) had normal transaminase levels (Control group). There were no significant difference in duration of fever, RR score, RDAI score, incidence of $O_2$ inhalation and duration of hospital stay between patient group and control group. We found 17 (60.7%) cases of RSV, 4 cases (14.3%) of parainfluenza, 4 cases (14.3%) of influenza B virus, 3 cases (10.7%) of adenovirus and 1 case (3.6%) of influenza A virus infection in patient group and 78 cases (56.9%) of RSV, 28 cases (20.4%) of parainfluenza virus, 13 cases (9.5%) of influenza A virus, 9 cases (6.6%) of influenza B virus, 6 cases (4.4%) of adenovirus and 3 cases (2.2%) of coxsackie virus infection in control group. Conclusion : There were 28 cases (17.0%) with elevated transaminase level among patients with virus isolated LRTI. There was no relation between elevated transaminase level and severity of disease. The viral etiologies in two groups were not significantly different. There was no significant difference of age distribution between two groups.

• BMB Reports
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• v.37 no.3
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• pp.376-382
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• 2004

The Epstein-Barr-transformed B lymphoblastoid cell lines, LCL, which express antigens, are potential antigen-presenting cells (APCs) for the induction of cytotoxic T lymphocytes in vitro. However, transfecting LCL with subsequent selection by antibiotics is notoriously difficult because the plating efficiencies of LCL are reported to be 1% or less. Therefore, this study investigated the optimal conditions for increasing the transduction efficiency of a recombinant adenovirus to LCL for use as a source of APCs. The transduction efficiencies were < 13% (SD $\pm$ 2.13) at a multiplicity of infection (MOI) of 100, while it was increased to 28% (SD $\pm$ 9.43) at an MOI of 1000. Moreover, its efficiencies to LCL that expressed the coxsackie adenovirus receptor were increased to 60% (SD $\pm$ 6.35) at an MOI of 1000, and were further increased to 70% (SD $\pm$ 4.56) when combined with the centrifugal method. The cationic liposome or anionic polymer had no effect on the transduction efficiency when compared to that of the centrifugal method. These results may be used as a convenient source of target cells for a CTL assay and/or autologous APCs for the induction of the in vitro CTL responses that are specific to viral and tumor antigens.