Combination therapy for treatment of viral infections
A virus infection, virus technology, applied in the direction of heterocyclic compound active ingredients, resistance to vector-borne diseases, medical preparations containing active ingredients, etc., can solve the problem of not obtaining animal models, etc.
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Embodiment 1
[0310] MDBK cells were infected with non-cytopathic (ncp) BVDV strain Pe515 at an MOI of 0.1 and passaged every three days with fresh medium. Stable infection was obtained after 6 passages. IFN (1000 U) and RBV (2 μM) were then added to the cells; this passage was denoted as passage 1 (P1). In addition, negative controls infected with mocks were established in the presence or absence of IFN (1000 U) or RBV (2 μM). Cells were passaged every 3 days at a 1:8 dilution into fresh medium containing the drug. At passage 3 (P3), the medium was supplemented with imino sugars and cells were cultured in the presence or absence of different concentrations of NB-DNJ (10, 50 and 100 μM), 100 μM 231 B and 50 μM NN-DNJ. Cells were passaged every three days with fresh medium containing drug. After another 9 passages (i.e., at passage 12), each sample was divided into the following three groups: Group 1, in which all drug combinations remained the same and cells were treated at the stated co...
Embodiment 2
[0341] As described in Example 1, MDBK cells were infected with non-cytopathic (ncp) BVDV strain Pe515 at an MOI of 0.1 and passaged every three days with fresh medium. Stable infection was obtained after 6 passages. IFN (1000 U) and RBV (2 μM) were then added to the cells; this generation was referred to as passage 1 (P1). In addition, negative controls infected with mocks were established in the presence and absence of IFN (1000 U) and RBV (2 μM). Cells were passaged every 3 days at a 1:8 dilution into fresh medium containing the drug. At passage 3 (P3) the medium was supplemented with NB-DNJ and the cells were cultured in the presence or absence of different concentrations of NB-DNJ (0.1, 1 and 10 μM). Cells were passaged every three days with fresh medium containing drug. After another 9 passages (i.e., at passage 12), each sample was divided into the following three groups: Group 1, in which all drug combinations remained the same and cells were treated at the stated c...
Embodiment 3
[0345]Bovine viral diarrhea virus (BVDV) is often used as a surrogate model for human hepatitis C virus (HCV). As members of the same family (flaviviruses), they share many similarities in genome organization, replication strategy and putative life span [1], see references listed below [1]. Prior to the development of cell culture HCV (HCVcc) infectivity systems, BVDV, as the closest related virus, was the preferred model system for studies that varied in their ability to recreate the entire infection cycle in cell culture. Although most aspects of HCV morphogenesis, viral secretion and reinfection can be studied in the HCVcc system, other aspects remain problematic; most notably the long-term culture of HCV-infected host cells. The latter requires the ability to conduct studies of viral clearance, emergence of viral escape mutants and, importantly, viral rebound after prolonged drug treatment cessation, with the aim of monitoring or improving clinical observations. In this r...
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