Mutations of the SARS-CoV-2 Spike Glycoprotein Detected in Cats and Their Effect on Its Structure and Function

Abstract

The high frequency of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) mutations and homology of the Angiotensin-Converting Enzyme-2 (ACE2) cell receptors in various hosts help the virus transcend species barriers. In this study, we investigated the mutations of the SARS-CoV-2 spike glycoprotein detected in cats and their effect on its structure and function. Interestingly, some of these mutations are reported here in cats for the first time. Structural analysis showed seven residue substitutions in the spike glycoprotein. Four of the detected mutations are located on the spike surface, which are critical interaction points for neutralizing antibodies. Furthermore, three of the reported mutations could facilitate viral binding to the ACE2 host receptor, influence S1/S2 cleavage, destabilize the β-hairpin structure of the S2 and enhance viral infectivity. Structural modeling and phylogenic analysis of the ACE2 receptor provided an indication of the binding capacity of the virus to the specific cell receptors of different species and hosts. The presented work highlights the effects of the residue substitutions on viral evasion, infectivity and possibility of SARS-CoV-2 spillover between humans and cats. In addition, the work paves the way for in-depth molecular investigation into the relationship between SARS-CoV-2 receptor binding and host susceptibility.

SARS‐CoV‐2 infection of companion animals in Egypt and its risk of spillover

“…We noticed that in our study SARS-CoV-2 infection rate in cats is higher than that in dogs, which agreed with previous studies (Barrs et al, 2020;Hamdy et al, 2022;Sit et al, 2020). Cats are more susceptible to SARS-CoV-2 than dogs (Hamdy et al, 2022;Hamer et al, 2021), which may be because of the high similarity of ACE2 receptor configuration in cats and humans (Hamdy et al, 2022;Hamer et al, 2021;Patterson et al, 2020;Ruiz et al, 2021;Sailleau et al, 2020). Besides, the viral persistence in cats (21 days) (Hamer et al, 2021) is longer than that in dogs (13 days) (Shi et al, 2020;Sit et al, 2020).…”

“…Even though only a partial spike gene was sequenced in this study, still 6 positive samples collected in December 2020 were identical to SARS‐CoV‐2 that was detected in human in Egypt during the same timeline that agreed with previous studies in Bosnia and Herzegovina (Goletic et al., 2022 ), France (Sailleau et al., 2020 ), China (Barrs et al., 2020 ), and the United Kingdom (Hosie et al., 2021 ). We noticed that in our study SARS‐CoV‐2 infection rate in cats is higher than that in dogs, which agreed with previous studies (Barrs et al., 2020 ; Hamdy et al., 2022 ; Sit et al., 2020 ). Cats are more susceptible to SARS‐CoV‐2 than dogs (Hamdy et al., 2022 ; Hamer et al., 2021 ), which may be because of the high similarity of ACE2 receptor configuration in cats and humans (Hamdy et al., 2022 ; Hamer et al., 2021 ; Patterson et al., 2020 ; Ruiz et al., 2021 ; Sailleau et al., 2020 ).…”

Interspecies transmission of SARS CoV-2 with special emphasis on viral mutations and ACE-2 receptor homology roles

“… It combined sometimes with N501Y mutation [ 64 ]. It was reported in SARS-CoV-2 that detected in cats in Egypt [ 3 ]. 5 S:K417 S:K417N S:K417T RBD It is associated with immune evasion [ 90 , 91 ].…”

“… This mutation is reported in Delta, Kappa and Epsilon variants [ 83 ]. It was reported in SARS-CoV-2 that detected in cats in Egypt [ 3 ]. 7 S:Y453F RDB It was a common mutation in mink in Denmark during the summer of 2020, thus, it may be an adaptive mutation in mink [ 100 , 101 ].…”

“…Zoonotic and reverse zoonotic transmission of SARS-CoV-2 could occur during common activities and interaction between humans and animals. A combination of the SARS-CoV-2 high mutation rate and the homology of cellular ACE2 receptors seem to enable SARS-CoV-2 to transcend species barriers and facilitate the viral transmission between humans and animals [ 3 ]. Therefore, studying susceptible, non-susceptible hosts, reservoirs and intermediate animals could give a better understanding for such virus and could help in predicting further outbreaks.…”