Evaluating the Virology and Evolution of Seasonal Human Coronaviruses Associated with the Common Cold in the COVID-19 Era

Abstract

Approximately 15-30% of all cases of the common cold are due to human coronavirus infections. More recently, the emergence of the more severe respiratory coronaviruses, SARS-CoV and MERS-CoV, have highlighted the increased pathogenic potential of emergent coronaviruses. Lastly, the current emergence of SARS-CoV-2 has demonstrated not only the potential for significant disease caused by emerging coronaviruses, but also the capacity of novel coronaviruses to promote pandemic spread. Largely driven by the global response to the COVID-19 pandemic, significant research in coronavirus biology has led to advances in our understanding of these viruses. In this review, we evaluate the virology, emergence, and evolution of the four endemic coronaviruses associated with the common cold, their relationship to pandemic SARS-CoV-2, and discuss the potential for future emergent human coronaviruses.

Keywords: COVID-19; common cold; coronavirus.

Figure 1

Coronavirus Structure. (A) Electron micrographs of HCoV-229E, HCoV-OC43, and SARS-CoV-2. (B) Coronavirus virion schematic of SARS-CoV-2 with labeled structural proteins and their respective functions. All images were adapted from the Centers for Disease Control and Prevention (CDC) via the Public Health Image Library (PHIL).

Figure 2

Genomic Organization of the Human Common Cold Coronaviruses and SARS-CoV-2. The genomes of alphacoronaviruses (blue) HCoV-229E and HCoV-NL63 and betacoronaviruses (black, green) SARS-CoV-2, HCoV-HKU1, and HCoV-OC43 are shown with open-reading frames (ORFs) labeled. A 5-kb scale bar is provided. The replicase polyproteins (pp1a and pp1ab) are shown in the box below and the maturation cleavage events mediated by the papain-like proteases (PLPs) and 3CLpro are indicated by the clear or black arrows. E, Envelope; M, Matrix; N, Nucleocapsid; S, Spike; RdRP, RNA-dependent RNA polymerase; Hel, Helicase; ExoN, Exonuclease; N7-MT, N7-methyltransferase; EndoU, Endonuclease; 2′-O-MT, 2′O-methyltransferase.

Figure 3

Coronavirus evasion of IFN-induction and response pathways. (A) Coronavirus proteins that inhibit IFN-induction targeting TBK-1 or IRF3 protein or transcription of IFN-β. (B) Coronavirus proteins that inhibit STAT1/2 in the IFN-response pathway.