In the first quarter of the 21st century, we are already facing the third emergence of a coronavirus outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic. Comparative genomics can inform a deeper understanding of the pathogenesis of COVID-19. Previous strains of coronavirus, SARS-CoV, and Middle-East respiratory syndrome-coronavirus (MERS-CoV), have been known to cause acute lung injuries in humans. SARS-CoV-2 shares genetic similarity with SARS-CoV with some modification in the S protein leading to their enhanced binding affinity toward the angiotensin-converting enzyme 2 (ACE2) receptors of human lung cells. This expert review examines the features of all three coronaviruses through a conceptual lens of comparative genomics. In particular, the life cycle of SARS-CoV-2 that enables its survival within the host is highlighted. Susceptibility of humans to coronavirus outbreaks in the 21st century calls for comparisons of the transmission history, hosts, reservoirs, and fatality rates of these viruses so that evidence-based and effective planetary health interventions can be devised to prevent future zoonotic outbreaks. Comparative genomics offers new insights on putative and novel viral targets with an eye to both therapeutic innovation and prevention. We conclude the expert review by (1) articulating the lessons learned so far, whereas the research is still being actively sought after in the field, and (2) the challenges and prospects in deciphering the linkages among multiomics biological variability and COVID-19 pathogenesis.

中文翻译：

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冠状病毒发病机理的分子基础：行星健康的比较基因组学方法，可预防21世纪人畜共患病的爆发。

在21世纪的第一季度，我们已经面临冠状病毒爆发的第三次爆发，即导致2019年冠状病毒病（COVID-19）大流行的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。比较基因组学可以帮助您更深入地了解COVID-19的发病机理。已知以前的冠状病毒，SARS-CoV和中东呼吸综合征-冠状病毒（MERS-CoV）株会导致人类急性肺损伤。SARS-CoV-2与SARS-CoV具有遗传相似性，但对S蛋白进行了一些修饰，导致它们与人肺细胞血管紧张素转化酶2（ACE2）受体的结合亲和力增强。这篇专家综述通过比较基因组学的概念镜头检查了所有三种冠状病毒的特征。尤其是，强调了SARS-CoV-2的生命周期，使其能够在宿主体内生存。人类对21世纪冠状病毒暴发的敏感性要求比较这些病毒的传播历史，寄主，宿主和病死率，以便可以设计出循证有效的行星健康干预措施，以防止未来的人畜共患病暴发。比较基因组学为治疗创新和预防提供了有关推定和新型病毒靶标的新见解。我们通过（1）阐明迄今为止的经验教训来结束专家评审，而该领域的研究仍在积极寻求中；（2）解密多组学生物学变异性与COVID-19发病机理之间的联系所面临的挑战和前景。