COVID-19: Understanding the Infectivity of SARS-CoV-2 in Humans and Animals

The novel coronavirus (SARS-CoV-2) has spread like wildfire among human populations around the world. But at the same time, certain animal species have also proven susceptible to coronavirus disease 2019 (COVID-19). A new study explains how the virus’s infectivity varies among individuals and species. With more than one million deaths to its name, the COVID-19 pandemic is the deadliest in recent decades. Numerous studies are striving to understand the origin of the SARS-CoV-2 coronavirus, its mode of action, the factors that influence its virulence, and, of course, to find preventive and therapeutic solutions. In this context, research has focused in particular on viral infectivity in different species or individuals. Indeed, while SARS-CoV-2 was originally transmitted to humans by bats (a theory that has yet to be confirmed), it can infect certain animals to varying degrees. For example, cats and ferrets can develop the disease, as can dogs to a lesser extent, while cattle, pigs, chickens, and ducks—as well as mice and rats—are not sentient beings that are susceptible to infection or are only slightly susceptible. Identifying changes in the virus’s tropism could help explain these differences in infectivity between species. This may involve the mechanism by which the virus enters the host’s target cells, the way cellular functions are hijacked to facilitate viral replication, the translational adaptation of viral proteins, or their ability to evade the immune response. The replication cycle is complex and highly variable. Researchers have focused on the first aspect—the mechanism by which SARS-CoV-2 enters cells and the ability of target cells to translate viral genetic material—as it relates to different animal species and their genomics. To initiate entry, the coronavirus must recognize the ACE2 protein on the surface of target cells using its S spike protein. The interaction of the S protein with ACE2 is critical for viral infection. For example, by changing four residues on the surface of rat ACE2, the rats become susceptible to SARS-CoV-2 infection. However, once the virus is inside the cytoplasm, the RNA of the viral particles must also be correctly translated. Indeed, differences in the use of viral codons influence translational efficiency. In particular, SARS-CoV-2 is especially well-adapted to tRNA levels in the upper respiratory tract and lung parenchyma, where viral load is consequently higher. According to the researchers, the RBD domain of the SARS-CoV-2 spike (S) protein can recognize the ACE2 receptor in ferrets, civets, cats, and dogs, but not in pigs, chickens, ducks, mice, and rats. Furthermore, the translational adaptation of SARS-CoV-2 in humans—and thus the virus’s translational efficiency—appears to be greater compared to other species, which would explain its high infectivity in human populations. The combination of these two factors—one structural (viral entry) and the other functional (utilization of viral material)—allows researchers to largely explain the virus’s infectivity across different animal species. Among the species studied, humans are the primary species in which SARS-CoV-2—whose viral material is both utilized and translated efficiently—interacts optimally with ACE2. However, these properties stem from only a few minor genetic differences. Spontaneous viral mutations could therefore fairly quickly increase the virus’s affinity and stability within different individuals and organisms. This is a development to monitor closely, given the emergence of new, more contagious viral strains in certain parts of the world in recent months.