Which mammalian species are at risk of being infected by SARS-CoV-2: an ACE2 perspective

Abstract

SARS-CoV-2 can transmit efficiently in humans, but it is less clear what other mammalian are at high risk of being infected. SARS-CoV-2 contain a Spike (S) protein that uses mammalian ACE2 receptors to mediate cell entry, a species with a human-like ACE2 receptor is therefore at risk of being infected by SARS-CoV-2. We compared between 131 mammalian ACE2 genes and 15 coronavirus S proteins. We showed that global similarity reflected by the phylogenetic relationship from ACE2 gene alignment is a poor predictor of high-risk mammals, whereas local ACE2 similarities at key binding sites highlight several high-risk mammals. Both SARS-CoV and SARS-CoV-2 likely have a bat origin; however, direct human transmission is unlikely due to their differences in ACE2 receptors, and various mammals share similar or better homologies in ACE2 receptor with humans. Furthermore, by comparing key binding sites at S protein of SARS-like coronaviruses in high-risk mammals, we found high similarities in S protein binding domains between SARS-CoV-2 and Pangolin-CoV but not Civets-CoV, and high similarities between SARS-CoV and Civets-CoV but not Pangolin-CoV. Hence, evolutionary adaptation of the bat virus in different intermediate hosts could allow it to acquire distinct high binding potential between S protein and human-like ACE2 receptors.

SARS-CoV-2 in animals: potential for unknown reservoir hosts and public health implications

“…The effective binding of SARS-CoV-2 S protein to the host receptor angiotensin-converting enzyme 2 (ACE2) is one of the critical prerequisites for infecting a particular species and therefore determines the host range (Zhai et al 2020). In other words, a species that possess human-like ACE2 receptor is at risk of getting infected with SARS-CoV-2 (Wei et al 2021). Understanding the conservation of ACE2 receptor and its expression pattern across different animal species may provide insight into the potential hosts of SARS-CoV-2 (Sun et al 2020).…”

“…Based on the ACE2 homology studies, the direct transmission of SARS-CoV-2 from bat to human beings are unlikely. However, the rapid adaptation of a bat SARS-like-CoV in different high-risk mammalian species that shares good ACE2 homology with human beings might allow the virus to acquire high binding potential with human-like ACE2 receptors (Wei et al 2021).…”

COVID-19 highlights the model dilemma in biomedical research

“…As expected, species with high homology in the receptor-binding domain of angiotensin-converting enzyme 2 (ACE2), such as ferrets and hamsters, are highly susceptible to SARS-CoV-2 (ref. 3 ). However, the lack of species-specific molecular tools and reagents makes the correlation to human pathomechanisms challenging.…”

Harnessing the Sars-cov-2 Spike Protein Binding Affinity to Ace2 Receptor Through Narcotinic Compounds Combined With Adjuvants: an in Silico Insight

“…Angiotensin-converting enzyme 2 (ACE2) contributes to viral cell entry through the interaction with S protein [13][14][15]. Finding a compound that can block the formation of the complex between the SARS-CoV-2 S protein receptor binding domain (RBD) and the ACE2 receptor or disrupt in RBD-ACE2 complex has been followed as a reasonable strategy to come up with a rational drug discovery for COVID-19 [16].…”