School of Life Sciences, Arizona State University, Tempe, Arizona, 85281.
Center for Evolution & Medicine, Arizona State University, Tempe, Arizona, 85281.
Evolution. 2020 Dec;74(12):2549-2559. doi: 10.1111/evo.14107. Epub 2020 Oct 27.
Following widespread infections of the most recent coronavirus known to infect humans, SARS-CoV-2, attention has turned to potential therapeutic options. With no drug or vaccine yet approved, one focal point of research is to evaluate the potential value of repurposing existing antiviral treatments, with the logical strategy being to identify at least a short-term intervention to prevent within-patient progression, while long-term vaccine strategies unfold. Here, we offer an evolutionary/population-genetic perspective on one approach that may overwhelm the capacity for pathogen defense (i.e., adaptation) - induced mutational meltdown - providing an overview of key concepts, review of previous theoretical and experimental work of relevance, and guidance for future research. Applied with appropriate care, including target specificity, induced mutational meltdown may provide a general, rapidly implemented approach for the within-patient eradication of a wide range of pathogens or other undesirable microorganisms.
在最近已知的感染人类的冠状病毒 SARS-CoV-2 广泛传播之后,人们开始关注潜在的治疗选择。由于尚未批准任何药物或疫苗,研究的一个重点是评估重新利用现有抗病毒治疗方法的潜在价值,逻辑策略是确定至少一种短期干预措施来阻止患者体内病情进展,同时展开长期疫苗策略。在这里,我们从进化/群体遗传学的角度来探讨一种可能会破坏病原体防御(即适应)诱导的突变崩溃的方法——提供关键概念的概述、相关理论和实验工作的回顾,以及对未来研究的指导。如果应用得当,包括靶向特异性,诱导突变崩溃可能为广泛的病原体或其他不良微生物在患者体内的根除提供一种通用的、快速实施的方法。