Novel approaches and challenges to treatment of central nervous system viral infections.

摘要: Existing and emerging viral central nervous system (CNS) infections are major sources of human morbidity mortality. Treatments proven efficacy currently limited predominantly to herpesviruses immunodeficiency virus (HIV). Development new therapies has been hampered by the lack appropriate animal model systems for some important viruses difficulty in conducting clinical trials diseases that may be rare, or case arboviral infections, often have variable seasonal geographic incidence. Nonetheless, many novel approaches antiviral therapy available, including candidate thiazolide pyrazinecarboxamide derivatives with potential broad-spectrum efficacy. New herpesvirus drugs include helicase-primase terminase inhibitors. The use antisense oligonucleotides other strategies interfere RNA translation shown experimental models CNS disease. Identifying specific molecular targets within replication cycles led existing agents will undoubtedly continue basis future drug design. A promising area research involves based on enhanced understanding host immune responses. Toll-like receptor agonists inhibit cytokines as well interferon preparations all therapeutic Passive transfer virus-specific cytotoxic T lymphocytes used humans provide an effective potentially progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against proteins developed several cases evaluated settings West Nile HIV infection pre-exposure prophylaxis rabies. Ann Neurol 2013;74:412–422