초록 ▼

◆ 바이러스 감염 제어용 생물소재(KW-200, JSC) 최적화 및 작용기작 연구
- 바이러스 타깃 단백질 (로타바이러스: VP4, 코로나바이러스: 3CL^pro, PL^pro)의 발현을 통한 assay 시스템 구축 및 운용
- 바이러스(로타, 코로나) 타깃에 대한 생리활성 검증을 통한 감염 제어용 생물소재 및 활성물질 확보
- 바이러스 감염 제어용 배당 및 유사배당 생물소재 및 활성물질의 생리활성 검증 및 후보물질 도출
‧ 로타바이러스(대표후보소재 : KW-200), 코로나

◆ 바이러스 감염 제어용 생물소재(KW-200, JSC) 최적화 및 작용기작 연구
- 바이러스 타깃 단백질 (로타바이러스: VP4, 코로나바이러스: 3CL^pro, PL^pro)의 발현을 통한 assay 시스템 구축 및 운용
- 바이러스(로타, 코로나) 타깃에 대한 생리활성 검증을 통한 감염 제어용 생물소재 및 활성물질 확보
- 바이러스 감염 제어용 배당 및 유사배당 생물소재 및 활성물질의 생리활성 검증 및 후보물질 도출
‧ 로타바이러스(대표후보소재 : KW-200), 코로나바이러스(대표후보소재 : 감태)

◆ 바이러스 감염 타깃 효소 저해제 상호작용 작용기작 연구를 통한 생물소재 개발
- 천연소재로부터 glycosidase, SARS-CoV, 3CL^pro 저해활성을 갖는 생물소재(8종) 및 chemical library(100여종) 확보
- 저해활성물질-효소 상호 작용기전 구명
- 타깃 단백질의 생산, 정제 및 단백질/저해제(Diplacone) 복합체 결정을 통한 구조분석 성공

◆ 바이러스 감염성 염증 제어용 생물소재(KR-300) 최적화 및 작용기작 연구
- 바이러스 감염에 의해 유발되는 염증반응을 저해할 수 있는 생물소재 탐색시스템 구축 및 운용을 통한 항염증 활성 소재 도출 (15종)
- 선정된 활성 천연소재로부터 생리활성물질의 분리, 정제 및 활성검증, 선도물질 도출
- 활성 배당체 및 유사배당체 소재를 이용하여 세포계(cell-based assay) 및 동물모델에서 생리활성 효능 검증, 작용기전 구명
- 1단계에서 도출한 항염증 활성소재 (JSC, KR-300)의 작용기작 규명
- 항염 활성소재 KR-300의 독성시험 및 표준 정량·정성분석법/대량생산공정 개발

◆ 바이러스 감염·염증 동물모델을 활용한 활성물질의 효능, 독성 및 안전성 평가
- 바이러스 감염 동물모델 개발
- 바이러스 감염 동물모델을 이용한 생물소재 (KW-200, JSC 등)의 항바이러스 효능 및 안전성 검증
- KR-300의 전임상 시험을 위한 독성시험

◆ 대표후보 소재 KW-200의 대량생산 기술개발 및 현장적용연구
- 전임상 및 임상연구 (축산용, 인체용)를 위해 이유자돈 모델을 활용한 KW-200의 경구 투여한 결과 증체율 및 소화 흡수율 증가, 설사감소의 효과를 나타냄

(출처 : 보고서 요약서 3p)

Abstract ▼

Ⅳ. Results
☞ The 1^st project : Optimization and action mechanism study of biomaterial (JSC, KW-200) for virus infection control
◆ Establishment and evaluation of assay system through the expression of the target viral protein (Rotavirus and Coronavirus)
⁃ The expression and purif

Ⅳ. Results
☞ The 1^st project : Optimization and action mechanism study of biomaterial (JSC, KW-200) for virus infection control
◆ Establishment and evaluation of assay system through the expression of the target viral protein (Rotavirus and Coronavirus)
⁃ The expression and purification of the rotavirus VP4 protein via insect cell expression system
⁃ The bulk expression and purification of the target enzyme (3CL^pro and PL^pro) for Coronavirus (SARS, BCoV, PEDV).
⁃ The establishment and evaluation of the bio-active inhibitor probing system and screening for the target viral proteins (VP4 and 3CL^pro)
◆ Establishment of the biomaterials and active compounds by the established assay systems of the target viral protein
⁃ The establishment of the biomaterials (KW-200, JSC) and active compounds (49) by the established assay screening system for Rotaviruses control
⁃ The establishment of the biomaterials (6) and active compounds (50) by building the bio-active inhibitor probing system and screening the target enzyme (3CL^pro and PL^pro) for Coronavirus control
⁃ Securing of 100 compounds library isolated from bio-materials by identification and structural analysis
⁃ Development of novel glycosyltransferase (28) for glycoside and the glycoside like substances of bio-active material by improved solubility
⁃ Establishment of the glycoside and the glycoside like substances library (over 30) by enzymatic and chemical synthesis
◆ Development of the safety of candidate materials and the mass production techniques
⁃ HPLC profiling of biomaterial (KW-20) and active substances bearing anti-viral activity
◆ The field test of the candidate material (KW-200)
⁃ Establishment of the field trials, as a result of the increased growth performance, digestibility and reduced diarrhea when the weanling pigs ate feed with KW-200

☞ The 2^nd project : Study of mutual interaction between inhibitor and enzyme targeting to virus infection
◆ Development of α-glucosidse inhibitors (55) from the biomaterials (Broussonetia papyrifera, Psoralea corylifolia, Garcinia mangostana, Paulownia tomentosa, Flemingia philippinensis, etc)
◆ Development of stylbene urea as novel competitive α-Glucosidse inhibitor
◆ Study of design and synthesis of Building Block for glycosid-like
◆ Development of SARS-CoV PL^pro inhibitors (15) from Lespedesa bicolor and Tribulus terrestris
◆ Isolation of bioactive substances (8) form Morus lhou targeting to protease (Aβ-secretase) inhibition
◆ Production and Purification technology of SARS-CoV PL^pro and its structural determination
◆ Structure determination of Clostridium perfringens neuraminidase in complex with geranylated flavonoids

☞ The 3^rd project : Study of optimization and biological mechanism on anti-inflammatory material (KR-300)
◆ Development and utilization of cell-based screening system for the new active bio-materials and substances with anti-inflammatory activity:
⁃ Screening system for the inhibitor of cell adhesion molecules like VCAM-1/VLA-4 and Sialic glycosaminoglycan/P-selectin
⁃ Screening system for the inhibitor of IL-6 signaling
⁃ Screening system for the inhibitor of Toll-like receptors
⁃ Found 15 active materials with anti-inflammatory activity among 500 materials
◆ Purify the active compounds from elicited bio-materials and determine the structure of the compounds :
⁃ Identification of 50 active compounds with anti-inflammatory activity from several bio-materials: Fallopia japonica, Tripterygium Regelii , Lithospermum erythrorhizon, Ecklonia cava, Angelica Utilis, Torreya nucifera, Glycyrrhiza uralensis, Alpinia katsumadai, Psoralea corylifolia, Curcuma longa, Piper nigrum, Saururus chinensis and so on.
⁃ Identification of TLR inhibitors including norkurarinol from Sophora flavescens
⁃ Identification of anti-inflammatory bio-material, KR-200 and KR-200 -glucoside from Fallopia japonica
⁃ Development of KR-300 showing anti-inflammatory activity through the inhibition of TLRs and IL-6 signaling
⁃ Isolation of KR-301 from KR-300 and determine the structure of KR-301
◆ Identify the biological target and the mechanism of the elicited compounds
⁃ Norkurarinol showed the anti-viral activity through the activation of IRF-3, followed by IFN-beta induction.
⁃ Demonstrate the anti-viral and anti-inflammatory effect of KR-200 after coxsackievirus A21 infection: KR-200 inhibit the NF-kB and AP-1 activation and inflammatory cytokine production induced by coxsackievirus A21 infection.
⁃ KR-300 and the active compounds from Psoralea corylifolia showed inhibition of IL-6 signaling.
⁃ KR-301 inhibits inflammation induced by TLR activation and viral infection through the direct binding with IKKα/β and NF-kB p50 complex and inhibition of their phosphorylation.
◆ Verify in vivo anti-inflammatory activity of the elicited compounds by using animal model
⁃ KR-200 and KR-300 inhibited the expression of proinflammaory cytokine (IL-1beta, IL-6, and TNF-alpha) and mRNA of inflammatory genes (COX-2 and NOS-II) in mice with inflammation.
⁃ KR-300 also ameliorated osteoarthritis.
◆ Increase the anti-inflammatory activity of the elicited bio-materials by modification such as synthesis and conversion of the active glycosides
◆ Analysis quantities and qualities of the active compounds.
◆ Safety study of the active materials or compounds for further practical use
◆ Development of mass-production process of the active materials for their application
◆ Conclusionally, we founds several compounds and materials with anti-inflammatory activity in this study and expect these materials are good candidates for the therapy of viral infection and systemic inflammation.

☞ The 4^th project : Studies on efficacy and mechanism of antiviral drugs in experimental animal models
◆ Evaluating the efficacy and safety of bio-materials in animal model
① 1st year
‧ Development of rotavirus animal model: Before evaluating the efficacy and safety of anti-rotavirus drug candidates, colostrum-deprived (Col-D) piglets were obtained from sows by hysterectomy and were inoculated with a porcine rotavirus strain for establishing a rotavirus animal model. Colostrum-deprived calves were also inoculated with a bovine rotavirus strain as a rotavirus animal model.
‧ Evaluation of efficacy and safety of anti-rotavirus drug candidate, EC: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, EC, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Determination of rotavirus and cell interaction: Using microarray system, increase or decrease of host genes in mock- or virus-infeced cells were determined.
‧ Analysis of full-length 11 genomic segments of rotaviruses: In order to analyze full-length 11 genomic segments of rotaviruses to be used for establishing rotavirus animal model, eleven genomic segments of various rotavirus strains were sequenced after RT-PCR and 5' and 3' RACE.
② 2nd year
‧ Evaluation of efficacy and safety of SW-100 in animal model as an antirotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Evaluation of efficacy and safety of JSC in animal model as an antirotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Evaluation of efficacy and safety, and synergistic effect by combination therapy of various mixtures of JSC and SW-100 in animal model as an antirotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
③ 3rd year
‧ Evaluation of efficacy and safety of methanol-extracted KW-200 in animal model as an antirotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Evaluation of anti-proimflammatory efficacy of methanol-extracted KW-200: To evaluate influence of KW-200 on mRNA expression levels of IL-8, IL-10, TNF-α, IFN-β, IFN-γ, NF-kB, p38, and JNK in Col-D piglets, real-time RT-PCR assays with primer pairs specific to IL-8, IL-10, TNF-α, IFN-β, IFN-γ, NF-kB, p38, and JNK was performed with the duodenum, jejunum, ileum and splenocytes sampled from each group.
‧ Safety assessment of methanol-extracted KW-200 in mice: In order to assess the safety of KW-200 in mice, mice were divided into mock-treated group, 1000 mg/kg orally treated group, 2000 mg/kg orally treated group, 5000 mg/kg orally treated group, 1000 mg/kg intra-peritoneally treated group, 2000 mg/kg intra-peritoneally treated group, and 5000 mg/kg intra-peritoneally treated group. Before administration, the weight of each mouse was measured. Each group consisting of 5 mice was reared for 2 weeks and were checked for abnormal clinical signs. At the termination of experiments, the weight of each mouse, each organ or tissue obtained by necropsy was measured. Before euthanasia, blood was collected from each experimental animal and were used for blood cell counts and blood chemistry.
‧ Safety assessment of methanol-extracted KW-200 in piglets: In order to assess the safety of KW-200 in piglets, piglets derived from sows by hysterotomy were divided into mock-treated group, 1000 mg/kg orally treated group, 2000 mg/kg orally treated group, 5000 mg/kg orally treated group, 1000 mg/kg intra-peritoneally treated group, 2000 mg/kg intra-peritoneally treated group, and 5000 mg/kg intra-peritoneally treated group. Before administration, the weight of each piglet was measured. Each group consisting of 2 piglets was reared for 2 weeks and were checked for abnormal clinical signs. At the termination of experiments, the weight of each piglet, each organ or tissue obtained by necropsy was measured. Before euthanasia, blood was collected from each experimental animal and were used for blood cell counts and blood chemistry.
‧ Evaluation of efficacy and safety of KW-200 fraction in animal model as an antirotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Evaluation of anti-proimflammatory efficacy of KW-200 fraction: To evaluate influence of KW-200 on mRNA expression levels of NF-kB, IL8, IFN-β and TNF-α in Col-D piglets, real-time RT-PCR assays with primer pairs specific to IL8, IL10, IFN-β, and TNF-α was performed with the duodenum, jejunum, ileum and splenocytes sampled from each group.
‧ Evaluation of efficacy and safety of glycyrrhizin in animal model as an antirotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups. ‧ Development of a new animal model with G9 bearing porcine rotavirus strain: G9 bearing rotaviruses are the fifth most predominant virus in humans. These viruses are found in only pigs among animals, suggesting it to be reservoir of human strains. In order to develop rotavirus animal model with G9 bearing strain, G9P[7] and G9P[23] strains isolated in swine were inoculated into Col-D piglets produced in sows by hysterotomy, and intestinal and extra-intestinal pathogenicity were evaluated.
④ 4th year
‧ Evaluation of efficacy and safety of compression-extracted KW-200 in animal model as an antirotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Evaluation of anti-proimflammatory efficacy of compression-extracted KW-200: To evaluate influence of compression-extracted KW-200 on mRNA expression levels of IL-8, IL-10, TNF-α, IFN-β, IFN-γ, NF-kB, p38, JNK in Col-D piglets, real-time RT-PCR assays with primer pairs specific to IL-8, IL-10, TNF-α, IFN-β, IFN-γ, NF-kB, p38, JNK was performed with the duodenum, jejunum, ileum and splenocytes sampled from each group.
‧ Safety assessment of compression-extracted KW-200 in mice: In order to assess the safety of KW-200 in mice, mice were divided into mock-treated group, 1000 mg/kg orally treated group, 2000 mg/kg orally treated group, 5000 mg/kg orally treated group, 1000 mg/kg intra-peritoneally treated group, 2000 mg/kg intra-peritoneally treated group, and 5000 mg/kg intra-peritoneally treated group. Before administration, the weight of each mouse was measured. Each group consisting of 5 mice was reared for 2 weeks and were checked for abnormal clinical signs. At the termination of experiments, the weight of each mouse, each organ or tissue obtained by necropsy was measured. Before euthanasia, blood was collected from each experimental animal and were used for blood cell counts and blood chemistry.
‧ Safety assessment of compression-extracted KW-200 in piglets: In order to assess the safety of KW-200 in piglets, piglets derived from sows by hysterotomy were divided into mock-treated group, 1000 mg/kg orally treated group, 2000 mg/kg orally treated group, 5000 mg/kg orally treated group, 1000 mg/kg intra-peritoneally treated group, 2000 mg/kg intra-peritoneally treated group, and 5000 mg/kg intra-peritoneally treated group. Before administration, the weight of each piglet was measured. Each group consisting of 2 piglets was reared for 2 weeks and were checked for abnormal clinical signs. At the termination of experiments, the weight of each piglet, each organ or tissue obtained by necropsy was measured. Before euthanasia, blood was collected from each experimental animal and were used for blood cell counts and blood chemistry.
‧ Reevaluation of efficacy and safety, and synergistic effect by combination therapy of various mixtures of JSC and SW-100 in animal model as an antirotavirus drug candidate: Due to small numbers of animals used, the reviewers suggested reevaluating efficacy and safety, and synergistic effect by combination therapy of various mixtures of JSC and SW-100 in animal model as an antirotavirus drug candidate at the 1st stage evaluation. In order to address the points raised by reviewers, the efficacy and safety of anti-rotavirus drug candidate were reevaluated using Col-D piglets. Experimental piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Safety assessment of various mixtures of JSC and SW-100 in mice: In order to assess the safety of various mixtures of JSC and SW-100 in mice, mice were divided into mock-treated group, 600 mg JSC plus 4.4 g/kg orally treated group, 800 mg JSC plus 7.2 g ST-100/kg orally treated group, 4 g JSC plus 12 g ST-100/kg orally treated group, 8 g JSC plus 24 g ST-100/kg orally treated group, 600 mg JSC plus 4.4 g/kg intraperitoneally treated group, 800 mg JSC plus 7.2 g ST-100/kg intraperitoneally treated group, 4 g JSC plus 12 g ST-100/kg intraperitoneally treated group, and 8 g JSC plus 24 g ST-100/kg intra-peritoneally treated group. Before administration, the weight of each mouse was measured. Each group consisting of 5 mice was reared for 2 weeks and were checked for abnormal clinical signs. At the termination of experiments, the weight of each mouse, each organ or tissue obtained by necropsy was measured. Before euthanasia, blood was collected from each experimental animal and were used for blood cell counts and blood chemistry.
‧ Safety assessment of various mixtures of JSC and SW-100 in piglets: In order to assess the safety of various mixtures of JSC and SW-100 in piglets, piglets derived from sows by hysterotomy were divided into mock-treated group, 600 mg JSC plus 4.4 g/kg orally treated group, 800 mg JSC plus 7.2 g ST-100/kg orally treated group, 4 g JSC plus 12 g ST-100/kg orally treated group, 8 g JSC plus 24 g ST-100/kg orally treated group, 600 mg JSC plus 4.4 g/kg intraperitoneally treated group, 800 mg JSC plus 7.2 g ST-100/kg intraperitoneally treated group, 4 g JSC plus 12 g ST-100/kg intraperitoneally treated group, and 8 g JSC plus 24 g ST-100/kg intra-peritoneally treated group. Before administration, the weight of each piglet was measured. Each group consisting of 2 piglets was reared for 2 weeks and were checked for abnormal clinical signs. At the termination of experiments, the weight of each piglet, each organ or tissue obtained by necropsy was measured. Before euthanasia, blood was collected from each experimental animal and were used for blood cell counts and blood chemistry.
‧ Reevaluation of efficacy and safety of methanol-extracted KW-200 in animal model as an antirotavirus drug candidate: Due to small numbers of animals used, the reviewers suggested reevaluating efficacy and safety of methanol-extracted KW-200 in animal model as an antirotavirus drug candidate at the 1st stage evaluation. In order to address the points raised by reviewers, the efficacy and safety of anti-rotavirus drug candidate were reevaluated using Col-D piglets. Experimental piglets were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated (various concentration) groups, and mock-inoculated and drug-treated (various concentration) groups. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, histological changes of small intestine and systemic organs, and antigen-distribution in small intestine and systemic organs were compared among above groups.
‧ Revaluation of anti-proimflammatory efficacy of methanol-extracted KW-200: To evaluate influence of compression-extracted KW-200 on mRNA expression levels of IL-8, IL-10, TNF-α, IFN-β, IFN-γ, NF-kB, p38, JNK in Col-D piglets, real-time RT-PCR assays with primer pairs specific to IL-8, IL-10, TNF-α, IFN-β, IFN-γ, NF-kB, p38, JNK was performed with the duodenum, jejunum, ileum and splenocytes sampled from each group.
⑤ 5th year
‧ Evaluation of efficacy of methanol-extracted KW-200 in calf model as an anti-rotavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D calves were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated group, and mock-inoculated and drug-treated group. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, and histological changes of small intestine and systemic organs were compared among above groups.
‧ Evaluation of efficacy of methanol-extracted KW-200 in calf model as an anti-coronavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus drug candidate, Col-D calves were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated group, and mock-inoculated and drug-treated group. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, and histological changes of small intestine and systemic organs were compared among above groups.
‧ Evaluation of efficacy of methanol-extracted KW-200 in calf model as an anti-rotavirus and anti-coronavirus drug candidate: In order to evaluate the efficacy and safety of anti-rotavirus and anti-coronavirus drug candidate, Col-D calves were randomly divided into mock-inoculated and mock-treated group, virus-inoculated and mock-treated group, virus-inoculated and drug-treated group, and mock-inoculated and drug-treated group. Mortality, abnormal clinical signs, fecal consistency, fecal virus shedding, and histological changes of small intestine and systemic organs were compared among above groups.
‧ Development of a new animal model with G5P[7] bearing porcine and bovine rotavirus strains: In order to choose the rotavirus strain which can induce diarrhea to piglelts and calves, G5P[7] bearing porcine and bovine rotavirus strains were selected and then inoculated into Col-D piglets produced in sows by hysterotomy and Col-D calves obtained from field farms, and intestinal and extra-intestinal pathogenicity were evaluated.

(출처 : SUMMARY 29p)

목차 Contents

• 표지 ... 1
• 제 출 문 ... 2
• 보고서 요약서 ... 3
• 요 약 문 ... 4
• SUMMARY ... 19
• CONTENTS ... 39
• 목차 ... 40
• 제1장 연구개발과제의 개요 ... 41
• 제2장 국내외 기술개발 현황 ... 70
• 제3장 연구개발수행 내용 및 결과 ... 75
• 제1절 연구개발 수행 내용 ... 75
• 제2절 연구개발 수행 결과 ... 84
• 제4장 목표달성도 및 관련분야에의 기여도 ... 648
• 제5장 연구개발결과의 활용계획 ... 667
• 제6장 연구개발과정에서 수집한 해외과학기술정보 ... 669
• 제7장 연구시설ㆍ장비 현황 ... 670
• 제8장 참고문헌 ... 671
• 끝페이지 ... 691