Since the emergence of MERS coronavirus (MERS-CoV) in 2012 and SARS-CoV-2 in 2019, NIAID scientists have advanced their understanding of how the viruses cause disease, focusing on developing animal models of disease and on countermeasures such as diagnostic tests and vaccine candidates. Research by NIAID scientists and others demonstrated that MERS-CoV and SARS-CoV-2 use their spike (S) protein to enter cells and initiate infection. After entering the cell, the viruses delay usual immune system responses, allowing the infection to gain a foothold. By the time the immune system responds, the infection has progressed and becomes much harder to fight.

Scientists also have characterized different strains of MERS-CoV and can determine through tests how those strains affect different animals. They also are studying how the stability of the virus changes in nature depending on the temperature and humidity where it exists and whether its form is liquid, droplet or aerosol. Using a monkey model of MERS, researchers have learned how the virus causes disease in people. For example, scientists at NIAID’s Rocky Mountain Laboratories (RML) demonstrated in a monkey model that clinical signs of MERS appear within 24 hours of infection. They also found that the virus causes disease deep within the lungs, leading to pneumonia. NIAID-funded researchers also have established several mouse models of infection that have been critical in developing MERS-CoV medical countermeasures.

A research group at RML also has developed a rhesus macaque model of SARS-CoV-2 to study COVID-19. The model mimics mild- to-moderate respiratory disease in people, including signs of pneumonia seen in an X-ray; this also is an important diagnostic feature in human patients. They also learned that the virus causes disease in the lungs, and that virus is shed from the nose, throat and rectum in a pattern similar to virus shedding in COVID-19 patients. The scientists are using this model to evaluate treatments and preventive vaccines.