In silico analysis of ACE2 orthologues to predict animal host range with high susceptibility to SARS-CoV-2

Abstract

SARS-CoV-2, which causes severe pneumonia epidemics, probably originated from Chinese horseshoe bats, but the intermediate and host range is still unknown. ACE2 is the entry receptor for SARS-CoV-2. The binding capacity of SARS-CoV-2 spike protein to ACE2 is the critical determinant of viral host range and cross-species infection. Here, we used an in silico approach to predict the potential animals range with high susceptibility to SARS-CoV-2 by modelling and studying the Spike–ACE2 interaction of 22 domestic and wild animals. Our results showed that all studied animals are potentially susceptible to SARS-CoV-2 infection with a slight difference in the binding affinity and stability of their ACE2–RBD complexes. Furthermore, we identified a specific substitution of tyrosine to histidine at position 41 in ACE2 that likely reduces the affinity to SARS-CoV-2 in horses and greater horseshoe bats. These results may help to provide important insights into SARS-CoV-2 host range which will make it possible to control the spread of the virus and identify animal models that could be used for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

Organoid Models of SARS-CoV-2 Infection: What Have We Learned about COVID-19?

“…The analysis of ACE2 protein conservation across species, the modelling of the S viral protein with ACE2 [195][196][197][198] and animal infection models [199][200][201][202][203][204][205][206][207][208][209][210][211] have highlighted the [170,171,[176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193][194]. Figure 5 was created with BioRender.com.…”

In Silico Screening of Natural Products as Potential Inhibitors of SARS-CoV-2 Using Molecular Docking Simulation

“…(24) Therefore, hACE2R might be another potential target for inhibiting the viral attachment with the host cells. (16)(17)(18) Our results demonstrate that amentoflavone, berbamine, betulinic acid, betulonic acid, cepharanthine, glucogallin, papyrifl avonol A, tomentin A and E exhibited good binding affinity with hACE2R protein, where amentoflavone and berbamine showed a strong binding capacity with this protein. Moreover, ABL1 and calcineurin-NFAT also play an important role in SARS-CoV-2 infection.…”

“…Molecular docking simulations were used to perform in silico screening of potential active compounds against hACE2R, 3CL PRO , PL PRO , RdRp, nsp10, nsp13-16, calcineurin-NFAT, transmembrane protease serine 2 (TMPRSS2), and ABL1. (16)(17)(18) In this respect, numerous plants containing high concentrations of flavonoids and polyphenolic compounds are known to have antioxidant, anticancer, anti-depressant, anti-infl ammatory, anti-diarrheal, antidiabetic, and anti-viral effects. Furthermore, a recent study showed that above mentioned compounds exert anti-SARS-CoV-2 activity with inhibitory concentration 50/effective concentration 50 less than 10 μmol/L.…”

Animal Transmission of SARS-CoV-2 and the Welfare of Animals during the COVID-19 Pandemic

“…With respect to ungulate species, three cervids were rated as having ACE2 receptor sequences with a high propensity for binding SARS-CoV-2, and 21 artiodactyls scored as medium (including domestic cattle, sheep, goats, and water buffalo) [150]. A similar study comparing ACE2 protein sequences in humans and 22 nonhuman animal species (including six ungulates) concluded that C. dromedarius and O. aries have a higher binding affinity to SARS-CoV-2 compared to humans, while alpaca (Vicugna pacos) have a binding affinity about equal to that of humans, and E. caballus and Przewalski's wild horse (Equus prezwalskii) have lower binding affinities [151].…”