ANTI-ORTHOPOXVIRUS DRUG DISCOVERY AND DEVELOPMENT

描述（改编自申请人摘要）：生物学的可能性 恐怖主义已经从想象的领域变成现实。 这一威胁 可以采取几种形式。 这种情况下最有可能的病原体之一 是天花 同样的特征使天花成为可怕的人类 病原体，包括气溶胶感染性和在人体宿主外的稳定性， 使其成为潜在的毁灭性生物武器 传播 天花在一个主要的人口中心可能会导致突然的，同时的 发生了数以千计的严重疾病。 的主要原因 这是因为现在很少有人能免受先前感染的影响 疫苗接种是1980年宣布完成 消灭天花。 此外，接种疫苗也没有什么好处。 向已经被恐怖分子释放病毒感染的人提供援助， 对暴露人群接种疫苗可能不会降低 预防二次传播。 疫苗供应和 质量也会妨碍大规模的疫苗接种工作。 因为这些 局限性，开发治疗天花的化学治疗剂 必须进行感染。 目前不存在这样的代理人。 解决 这一需要，该提案提出了开发药物的计划， 在感染时抑制由天花病毒编码的酶。 重点 将主要作用于核苷和核苷酸， 新陈代谢. 一个由三名化学家和两名病毒学家组成的联盟， 领导人和一名病毒学家顾问已经为此到位 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.