Therapeutics for Pox, Filo and Other Viral Pathogens

描述（由申请人提供）：生物恐怖主义的可能性已经从猜测的领域变成了现实。因此，国家过敏和传染病研究所已经确定了一些构成最大威胁的物质，并建议开发针对它们的治疗药物。这类病原体包括天花和病毒性出血热（包括埃博拉和马尔堡丝状病毒）。为准备可能的天花释放，正在制定计划，为大量人群提供足够数量的天花疫苗。然而，在这一人群中，有些人无法耐受疫苗，或者由于先前的健康和/或年龄原因，不适合接受疫苗保护。因此，由于这些和其他原因，NIAID推荐了治疗剂的开发。本建议涉及这一方向的两个治疗目标：(i)在疫苗无效、无法获得或因上述原因未接种的情况下治疗天花感染的药物，以及（ii）在接种疫苗时抵消疫苗效果的药物。对于丝状病毒埃博拉病毒和马尔堡病毒，它们的表现与天花不同，但仍然产生可怕的影响，目前没有感染前疫苗，也没有感染后治疗方法。为了解决这些情况，人们计划设计和开发药物，通过抑制这些病毒感染后的病毒复制步骤来起作用。重点将放在主要影响核酸代谢的核苷和核苷酸上。为此目的成立了一个由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，可以预期将发现有希望的抗正痘病毒和抗丝状病毒药物。

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.