A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses

Abstract

Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much more than serological or antigenic variants, resulting in the effective presence of two distinct viruses. Here, we review the distinct differences in the S proteins of these viruses, which are likely to translate into distinct biological outcomes. We introduce a new concept related to the non-taxonomical classification and differentiation among FCoVs by analyzing and comparing the genetic, structural, and functional characteristics of FCoV and the FCoV S protein among the two serotypes and FCoV biotypes. Based on our analysis, we suggest that our understanding of FIP needs to consider whether the presence of these two distinct viruses has implications in clinical settings.

Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop

“…proteins of viruses belonging to the Alphacoronavirus and Gammacoronavirus genera [40,44]. Considering that this region is proteolytically sensitive and has been shown to play a major role in the S protein function in other CoVs, the use of in silico modeling tools has become a useful alternative to study this region in the context of the structural organization of the protein [37,38]. The SARS-CoV-2 S protein is not an exception to this issue and the recently reported structures do not allow resolution of the S1/S2 priming loop and/ or have the loop mutated.…”

“…IBV) [40]. It is noticeably absent in most Alphacoronaviruses, with the clear exception of type I canine and feline coronaviruses [28,37]. One feature of the distinct insert for of SARS-CoV-2 that warrants attention relates to potential changes as the virus evolves.…”

“…The analysis of modeled proteins provides a powerful tool to identify predicted structural characteristics, which can translate into structure-function changes in the studied protein. Our laboratory has previously taken advantage of these tools, for structure-function studies of other CoVs S proteins [23,37,38]. To perform the modeling, it is first necessary to identify a suitable protein structure to be used as template, which will determine the accuracy of the predicted model.…”

“…Solving the structure of the S1/S2 site was also found to be an issue in the SARS-CoV S structure we used for our modeling analyses. We have previously shown that the S1/S2 site can be modeled in other CoV S proteins, and it appears to be organized as a flexible exposed loop that extends from the S structure and suggest it could be easily accessible for proteolytic activation [37].…”

The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak

“…It is reasoned that the lung epithelial cells are the primary target of the virus. Thus, it has been reported that human-to-human transmissions of SARS-CoV occurs by the binding between the receptor-binding domain of virus spikes and the cellular receptor which has been identified as angiotensin-converting enzyme 2 (ACE2) receptor [20,22]. Importantly, the sequence of the receptor-binding domain of COVID-19 spikes is similar to that of SARS-CoV.…”