Two highly pathogenic human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), have emerged in the past decade. The lack of any clinically approved antiviral treatments or vaccines for either virus emphasizes the importance of the design of effective therapeutics and preventives.
Bats have been implicated as reservoirs of both SARS-CoV and MERS-CoV as well as related viruses and other human coronaviruses (HCoVs), such as HCoV-229E and HCoV-NL63. The dispersion of bat species over much of the globe probably enhances their potential to act as reservoirs for pathogens, some of which are extremely virulent and potentially lethal to other animals and humans.
Multiple animal models for SARS-CoV infection exist, although mouse models have been the most thoroughly characterized. Mouse-adapted SARS-CoV is capable of causing pathology that is representative of human infections in both young and aged animals.
Small animal models for MERS-CoV infection have not yet been reported, although the possibility of further ongoing selection in the receptor-binding sequence in the spike protein or other sequences that are important for host specificity might contribute to this limitation. A mild disease phenotype that can include either localized or widespread pneumonia is observed in inoculated macaques.
Multiple vaccine strategies have been attempted with coronaviruses, mostly (but not exclusively) targeting the spike glycoprotein. Successful live-attenuated vaccines have utilized reverse genetic strategies to delete the envelope protein or inactivate the exonuclease activity of non-structural protein 14 (nsp14) .
MERS-CoV, similarly to SARS-CoV in 2003, has the potential to have a profound impact on the human population; however, its low penetrance thus far suggests that the virus might either ultimately fail to develop a niche in humans or it might still be adapting to human hosts and that the worst of its effects are yet to come.
Coronavirus phylogeny shows an incredible diversity in antigenic variants, which leads to limited cross-protection against infection with different strains, even within a phylogenetic subcluster. Consequently, the risk of introducing novel coronaviruses into naive human and animal populations remains high.
The emergence of severe acute respiratory syndrome (SARS) coronavirus and, more recently, Middle East respiratory syndrome (MERS) coronavirus has highlighted the pathogenic and epidemic potential of this virus family. Here, Graham, Donaldson and Baric review key biological properties of coronaviruses and how to target them with potential therapeutics.
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.