Sialic Acid Receptors: The Key to Solving the Enigma of Zoonotic Virus Spillover

Emerging viral diseases are a major threat to global health, and nearly two-thirds of emerging human infectious diseases are zoonotic. Most of the human epidemics and pandemics were caused by the spillover of viruses from wild mammals. Viruses that infect humans and a wide range of animals have historically caused devastating epidemics and pandemics. An in-depth understanding of the mechanisms of viral emergence and zoonotic spillover is still lacking. Receptors are major determinants of host susceptibility to viruses. Animal species sharing host cell receptors that support the binding of multiple viruses can play a key role in virus spillover and the emergence of novel viruses and their variants. Sialic acids (SAs), which are linked to glycoproteins and ganglioside serve as receptors for several human and animal viruses. In particular, influenza and coronaviruses, which represent two of the most important zoonotic threats, use SAs as cellular entry receptors. This is a comprehensive review of our current knowledge of SA receptor distribution among animal species and the range of viruses that use SAs as receptors. SA receptor tropism and the predicted natural susceptibility to viruses can inform targeted surveillance of domestic and wild animals to prevent the future emergence of zoonotic viruses.