A decade after SARS: strategies for controlling emerging coronaviruses

Abstract

Two novel coronaviruses have emerged in humans in the twenty-first century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and are associated with high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains is a research priority. In this Review, we describe the emergence and identification of novel human coronaviruses over the past 10 years, discuss their key biological features, including tropism and receptor use, and summarize approaches for developing broadly effective vaccines.

Figure 1. Whole-genome phylogeny of representative coronaviruses.

The full genomic sequences of 50 coronaviruses were aligned and phylogenetically compared. Three distinct phylogenetic groups are shown: alphacoronaviruses (green), betacoronaviruses (blue) and gammacoronaviruses (orange). This taxonomical nomenclature replaced the former group 1, 2 and 3 designations, respectively. Deltacoronavirusesare newly characterized and are not shown. Classic subgroup clusters are marked as 2a–2d for the betacoronaviruses and 1a and 1b for the alphacoronaviruses. The tree was generated using maximum likelihood with the PhyML package. The scale bar represents nucleotide substitutions. Only nodes with bootstrap support above 70% are labelled. PowerPoint slide

Figure 2

Timeline of coronavirus emergence events

Figure 3. Changing viral ecology in expanding human and animal populations.

Alphacoronaviruses and betacoronaviruses have historically been shown to have the capacity to utilize orthologous receptors and carbohydrates for entry in different species. Thus, in host pools (bats, blue; domestic animals, red; and humans, green), viruses that are capable of cross-species transmission might exist or be generated by the intrinsic error rate of the RNA-dependent RNA polymerase. Bat populations that are largely separated from human and domestic animal populations result in limited viral emergence into new populations (part a). However, the expansion of human populations into previously unsettled areas, intensive domestic animal farm management practices that result in increased herd and flock sizes in small areas and in closer proximity to their human caretakers, and the encroachment of bats into human-populated regions contribute to the increased incidence of pathogenic human viruses from zoonotic pools (part b). PowerPoint slide