Therapeutics for Pox, Filo and Other Viral Pathogens

描述(申请人提供)：生物恐怖主义的可能性已从猜测领域变为现实。因此，国家过敏和传染病研究所确定了一些构成最大威胁的制剂，并建议开发针对它们的治疗剂。这组病原体包括天花和病毒性出血热(包括丝状病毒埃博拉和马尔堡病毒)。为应对可能出现的天花疫情，目前正在制定计划，为大量人口提供足够数量的天花疫苗。然而，在这一人群中，有一些人将无法耐受疫苗，或者由于先前存在的健康和/或年龄原因，将不适合接受疫苗保护。因此，由于这些和其他原因，NIAID建议开发治疗剂。这项提案涉及这一方向的两个治疗目标：(1)在疫苗无效、不可用或由于上述原因不能接种的情况下，用于治疗天花感染的药物；(2)在接种疫苗时抵消接种效果的药物。对于埃博拉和马尔堡丝状病毒，它们的表现与天花不同，但仍会产生可怕的影响，目前既没有感染前疫苗，也没有感染后治疗方法。为了解决这些情况，提出了设计和开发药物的计划，这些药物将在感染这些病毒后通过抑制病毒复制步骤发挥作用。重点将放在主要影响核酸代谢的核苷和核苷酸上。为此成立了一个由3名化学家和10名病毒学家组成的联盟。由于这组化学家和病毒学家已经进行了一段时间的广泛合作，可以预期有希望的抗正痘病毒和抗丝状病毒药物将被发现。

DESCRIPTION (provided by applicant): The possibility for biological terrorism has moved from the realm of speculation into reality. As a consequence, the National Institute of Allergy and Infectious Diseases has identified a number of agents that pose the greatest threat and has recommended that therapeutic agents be developed against them. Among that group of pathogens are smallpox and the viral hemorrhagic fevers (including the filoviruses Ebola and Marburg). In preparation for possible release of smallpox, plans are well underway to avail sufficient quantities of smallpox vaccine for a large number of people. However, within this population, there are individuals who will not be able to tolerate the vaccine or, for pre-existing health and/or age reasons, will not be suitable to receive vaccine protection. Thus, for these and other reasons, therapeutic agent development has been recommended by the NIAID. This proposal deals with two therapeutic goals in this direction: (i) agents for treating smallpox infection for instances where the vaccine was ineffective, not available or not administered for reasons just outlined, and (ii) drugs to counteract the effects of vaccination when administered. For the filoviruses Ebola and Marburg, which manifest themselves differently than smallpox but still produce horrendous effects, there are currently no pre-infection vaccines nor post-infection therapeutics available. To address these situations, plans are put forth for designing and developing drugs that would act by inhibiting viral replicative steps following infection by these viruses. Focus will be on nucleosides and nucleotides that affect, primarily, nucleic acid metabolism. A consortium of 3 chemists and 10 virologists has been assembled for this purpose. Because of the extensive collaborations that have been ongoing for some time by this group of chemists and virologists, it can be expected that promising anti-orthopoxvirus and anti-filovirus agents will be uncovered.