Prathapan Praveen
New Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Med Drug Discov. 2022 Jun;14:100120. doi: 10.1016/j.medidd.2022.100120. Epub 2022 Jan 24.
While antimicrobial drug development has historically mitigated infectious diseases that are known, COVID-19 revealed a dearth of 'in-advance' therapeutics suitable for infections by pathogens that have not yet emerged. Such drugs must exhibit a property that is antithetical to the classical paradigm of antimicrobial development: the ability to treat infections by any pathogen. Characterisation of such 'pan-pathogen' antimicrobials requires consolidation of drug repositioning studies, a new and growing field of drug discovery. In this review, a previously-established system for evaluating repositioning studies is used to highlight 4 therapeutics which exhibit pan-pathogen properties, namely azithromycin, ivermectin, niclosamide, and nitazoxanide. Recognition of the pan-pathogen nature of these antimicrobials is the cornerstone of a novel paradigm of antimicrobial development that is not only anticipatory of pandemics and bioterrorist attacks, but cognisant of conserved anti-infective mechanisms within the host-pathogen interactome which are only now beginning to emerge. Ultimately, the discovery of pan-pathogen antimicrobials is concomitantly the discovery of a new class of antivirals, and begets significant implications for pandemic preparedness research in a world after COVID-19.
虽然抗菌药物的研发在历史上减轻了已知的传染病,但新冠疫情揭示了缺乏适用于尚未出现的病原体感染的“预先”治疗方法。这类药物必须具备一种与传统抗菌药物研发范式相悖的特性:能够治疗任何病原体引起的感染。对这类“泛病原体”抗菌药物的特性描述需要整合药物重新定位研究,这是一个新兴且不断发展的药物发现领域。在本综述中,一个先前建立的评估重新定位研究的系统被用于突出显示4种具有泛病原体特性的治疗药物,即阿奇霉素、伊维菌素、氯硝柳胺和硝唑尼特。认识到这些抗菌药物的泛病原体性质是抗菌药物研发新范式的基石,这一范式不仅能够预测大流行和生物恐怖袭击,而且认识到宿主-病原体相互作用组中保守的抗感染机制,而这些机制直到现在才开始显现。最终,泛病原体抗菌药物的发现同时也是一类新型抗病毒药物的发现,并且对新冠疫情之后的世界大流行防范研究具有重大意义。