Origin and evolution of pathogenic coronaviruses

Coronaviruses cause respiratory and intestinal infections in animals and humans 1 . They were not considered to be highly pathogenic to humans until the outbreak of severe acute respiratory syndrome (SARS) in 2002 and 2003 in Guangdong province, China 2-5 , as the coronaviruses that circulated before that time in humans mostly caused mild infections in immunocompetent people. Ten years after SARS, another highly pathogenic coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Middle Eastern countries 6 . SARS coronavirus (SARS-CoV) uses angiotensin-converting enzyme 2 (ACE2) as a receptor and primarily infects ciliated bronchial epithelial cells and type II pneumocytes 7,8 , whereas MERS-CoV uses dipeptidyl peptidase 4 (DPP4; also known as CD26) as a receptor and infects unciliated bronchial epithelial cells and type II pneumocytes SARS-CoV and MERS-CoV were transmitted directly to humans from market civets and dromedary camels, respectively Extensive studies of these two important coronaviruses have not only led to a better understanding of coronavirus biology but have also been driving coronavirus discovery in bats globally In this Review, we focus on the origin and evolution of SARS-CoV and MERS-CoV. Specifically, we emphasize the ecological distribution, genetic diversity, interspecies transmission and potential for pathogenesis of SARS-related coronaviruses (SARSr-CoVs) and MERS-related coronaviruses (MERSr-CoVs) found in bats, as this information can help prepare countermeasures against future spillover and pathogenic infections in humans with novel coronaviruses.

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