Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the recent pandemic COVID-19, is reported to have originated from bats, with its intermediate host unknown to date. Here, we screened 26 animal counterparts of the human ACE2 (hACE2), the receptor for SARS-CoV-2 and SARS-CoV, and found that the ACE2s from various species, including pets, domestic animals and multiple wild animals, could bind to SARS-CoV-2 receptor binding domain (RBD) and facilitate the transduction of SARS-CoV-2 pseudovirus. Comparing to SARS-CoV-2, SARS-CoV seems to have a slightly wider range in choosing its receptor. We further resolved the cryo-electron microscopy (cryo-EM) structure of the cat ACE2 (cACE2) in complex with the SARS-CoV-2 RBD at a resolution of 3 Å, revealing similar binding mode as hACE2 to the SARS-CoV-2 RBD. These results shed light on pursuing the intermediate host of SARS-CoV-2 and highlight the necessity of monitoring susceptible hosts to prevent further outbreaks.

Cross-species recognition of SARS-CoV-2 to bat ACE2

“…Guo et al ( 30 ) reported that ACE2 genes showed high polymorphism among the R. sinicus populations, and R. sinicus ACE2 variants possessed different susceptibility to SARS-related-CoV infection. In the present study, together with the results from our previous work, our data showed that R. sinicus ACE2 could not bind to SARS-CoV-2 RBD ( 34 ). Zhao and colleagues ( 15 ) also reported R. sinicus ACE2 could not bind to SARS-CoV-2 RBD, although another report showed positive binding between R. sinicus ACE2 and SARS-CoV-2 RBD ( 13 ).…”

Backward transmission of COVID-19 from humans to animals may propagate reinfections and induce vaccine failure

“…As a consequence, a diverse range of vertebrates can be potentially infected by SARS-CoV-2 via their ACE2 receptors. This assumption is supported by the findings of ACE2 receptors in over 400 vertebrate species including both domestic and wild animals (Damas et al 2020 ; Wu et al 2020 ). SARS-CoV-2 infections have been recently confirmed in mammals including cats, monkeys, ferrets and hamsters (Santini and Edwards 2020 ).…”

“…Lau et al ( 2020 ) further showed that the entire genome of SARS-CoV-2 is most closely related to the SARSr-Ra-BatCoV RaTG13 from an intermediate horseshoe bat, except for its receptor-binding domain which is closest to pangolin-SARSr-CoVs, suggesting that SARS-CoV-2 is a recombinant virus. Overall, these findings indicate the complex origin of SARS-CoV-2, where evolutionary recombination and strong purifying selection occurred between strains from distinct host species before it spilled over to humans (Li et al 2020 ; Wu et al 2020 ; Sallard et al 2020 ). The back-and-forth transmission between human and wild species, when it occurs, may further enhance the genetic diversity of the virus.…”

“…Also, SARS-CoV-2 shares 96.2% of its sequences with a bat coronavirus isolated from Rhinolophus affinis , suggesting that bats may be the natural hosts of SARS-CoV-2 (Lu et al 2020 ; Paraskevis et al 2020 ; Zhou et al 2020 ). Cats, ferrets, minks, pangolins, snakes and turtles have been postulated as intermediate hosts of the novel coronavirus (Ji et al 2020 ; Li et al 2020 ; Nabi et al 2020 ; Wu et al 2020 ). Here we show that COVID-19 transmission from humans to animals is likely to amplify mutations and, in turn, to re-infect humans with deadlier mutants.…”

“…The infection of SARS-CoV-2 is induced by interactions between the SARS-CoV-2 receptor-binding domain and angiotensin-converting enzyme 2 (ACE2) receptor proteins (Santini and Edwards 2020 ; Wu et al 2020 ; Zhou et al 2020 ). As a consequence, a diverse range of vertebrates can be potentially infected by SARS-CoV-2 via their ACE2 receptors.…”