Development of animal models against emerging coronaviruses: From SARS to MERS coronavirus

Abstract

Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV.

Keywords: Animal models; Coronaviruses; MERS-CoV; Receptor; SARS-CoV.

Fig. 1

Schematic of strategies to develop an animal model to meet the FDA Animal Efficacy Rule. Under the FDA׳s Animal Efficacy Rule (“Animal Rule”) therapeutics against rare, emerging, or virulent agents can achieve regulatory approval provided efficacy is demonstrated in two animal models (one of which must be a non-rodent species). Animal species of interest must first be evaluated for permissiveness to viral replication and presentation of clinical disease. As an alternative, in animal species that are permissive but do not show clinical disease, serial passage can be performed. After an animal model has been developed the resulting disease must be characterized. The ideal animal model is permissive to infection and reproduces the clinical illness and pathology observed in humans.