ANTI-ORTHOPOXVIRUS DRUG DISCOVERY AND DEVELOPMENT

描述(改编自申请者的摘要)：生物学的可能性 恐怖主义已经从投机领域变成了现实。这一威胁 可以有几种形式。在这种情况下最有可能的病原体之一 就是天花。同样的特征使天花成为可怕的人类 病原体，包括气溶胶的传染性和人体外的稳定性， 使其成为潜在的毁灭性生物武器。传播 一个主要人口中心的天花可能会导致突然的、同时的 发生数以千计的重病病例。其主要原因是 这就是说，现在很少有人能免受前病毒的感染。 疫苗接种作为1980年宣布完成的结果 根除天花。此外，接种疫苗不会有什么好处。 对已经被恐怖分子感染的人释放病毒并立即 接触人群接种疫苗可能不会降低病毒的传染性 防止二次传播的原发病例。疫苗供应情况和 质量也将阻止大规模的疫苗接种努力。正因为如此 抗击天花的化疗药物的局限性和发展 必须进行感染。目前不存在这样的代理。致信地址 这一需求，这项提案提出了开发药物的计划，这些药物通过 在感染时抑制天花病毒编码的酶。焦点 将主要作用于核苷和核苷酸，主要是核酸 新陈代谢。由三名化学家和两名病毒学家组成的联盟作为项目 领导人和一名病毒学家顾问已经就位 目的。

DESCRIPTION (adapted from applicant's abstract): The possibility of biological terrorism has moved from the realm of speculation into reality. This threat can take several forms. One of the most likely pathogens in such a scenario is smallpox. The same characteristics that made smallpox a dreaded human pathogen, including aerosol infectivity and stability outside a human host, make it a potentially devastating biological weapon. Dissemination of smallpox in a major population center could result in the sudden, simultaneous occurrence of thousands of cases of severe illness. The primary reason for this is that so few people are now protected from infection by prior vaccination as a consequence of the declaration in 1980 of the complete eradication of smallpox. Furthermore, vaccination would be of little benefit to persons already infected by terrorist release of the virus and immediate vaccination of the exposed population might not reduce the infectivity of primary cases to prevent secondary transmission. Vaccine availability and quality would also prevent a massive vaccination effort. Because of these limitations, development of chemotherapeutic agents to combat smallpox infection must be undertaken. No such agents currently exist. To address this need, this proposal presents plans for developing drugs that act by inhibiting the enzymes encoded by the smallpox virus upon infection. Focus will be on nucleosides and nucleotides that effect, primarily, nucleic acid metabolism. A consortium of three chemists and two virologists as project leaders, and a virologist consultant, has been put into place for this purpose.