Interacting Proteins, Polymorphisms and the Susceptibility of Animals to SARS-CoV-2

Abstract

COVID-19, caused by SARS-CoV-2, is a world-wide problem for the human population. It is known that some animal species, such as mink, can become infected and transmit the virus. However, the susceptibility of most animals is not known. Here, we review the use of sequence analysis of the proteins which are known to interact with SARS-CoV-2 as a way to estimate an animal’s susceptibility. Although most such work concentrates on the angiotensin-converting enzyme 2 receptor (ACE2), here TMPRSS2 (Transmembrane Serine Protease 2), neuropilin-1 and furin are also considered. Polymorphisms, especially ones which are known to alter viral/host interactions are also discussed. Analysis of ACE2 and TMPRSS2 protein sequences across species suggests this approach may be of some utility in predicting susceptibility; however, this analysis fails to highlight some susceptible animals such as mink. However, combined with observational data which emerges over time about which animals actually become infected, this may, in the future, be a useful tool to assist the management of risks associated with human/animal contact and support conservation and animal welfare measures.

Efficacy of COVID-HIGIV in animal models of SARS-CoV-2 infection

“…Thus, this model may more closely mimic more severe disease in humans 37 – 40 . Since wild type mice are not susceptible to SARS-CoV-2 infection as the SARS-CoV-2 spike protein lacks affinity to mouse ACE2, required for the entry of the virus 41 , 42 , a variety of mouse models have been developed where the mice express the human ACE2 (hACE2) via genetic manipulation 43 – 45 or viral transduction 35 . Mouse-adapted SARS-CoV-2 viral strains have also been developed to study infection in wild type mice 46 , 47 .…”

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

“…Polymorphisms are genetic code variations shared by many individuals and can confer evolutionary advantage or disadvantage through natural selection. In regard to the novel coronavirus, there are two mammalian proteins that are key to viral susceptibility: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TM-PRSS2) [66,67]. ACE2 is a transmembrane protein on lung cell and other tissue surfaces that acts as the SARS-CoV-2 viral receptor and allows viral endocytosis [67,68].…”

“…In regard to the novel coronavirus, there are two mammalian proteins that are key to viral susceptibility: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TM-PRSS2) [66,67]. ACE2 is a transmembrane protein on lung cell and other tissue surfaces that acts as the SARS-CoV-2 viral receptor and allows viral endocytosis [67,68]. Although the specific effects of TMPRSS2 on SARS-COV-2 are not fully understood, it is thought to activate the virus' characteristic spike protein as a requisite step for endocytosis [69].…”

“…There is limited research on mustelid susceptibility to SARS-CoV-2 and how variations in TMPRSS2 may affect this. One recent review paper noted that at least one of the many protein sequences in TMPRSS2 that has been identified as important in the protease's facilitation of SARS-CoV-2 entry into human cells shows a number of polymorphisms in ferrets, which may explain some of why this particular mustelid species is not as affected by the virus as is its mink cousin [67] (as discussed below).…”

“…However, the differences between canine and mink amino acid sequences involved in ACE2 receptor binding domains may be sufficient to block SARS-CoV-2 entry into the cell, since the two species have shown some differences in susceptibility to this virus (see Section 2.6 below). In their review, Hancock et al [67] also constructed phylogenetic trees based on similarities in protein sequences composing both the ACE2 receptor and TMPRSS2 and found that the species that shared the most amino acid sequences for this receptor and protease were also the species that to date have tested positive for SARS-CoV-2 (e.g., ferrets, mink, cats, tigers, and dogs).…”