In Silico Assessment for Risk of Possible Human Transmission of FCoV-23

Abstract

Since the pandemic in 2019, coronaviruses (CoVs) have been a great concern for public health burden. The fact that CoVs can infect all animals including domestic ones and livestock points to a future pandemic even though interaction between human and wildlife animals is restricted. Moreover, interspecies transmission abilities of CoVs by mutations make them drastically risky not only for humans but also for animal health. Recently, a new CoV outbreak in cats in Cyprus, the so-called FCoV-23, has been realized. In addition to worries over animal health, any possible transmission to humans is now controversial. However, there have been limited characterization studies on FCoV-23. Thus, we aimed to assess the possible transmission of FCoV-23 to humans using in silico prediction tools. Accordingly, we first checked the binding affinities of receptor binding domain (RBD) of FCoV-23 against feline target protein and its human homolog. Next, we randomly and rationally created mutations on the RBD sequence and evaluated the binding affinities using protein docking tools. Our results underlined that multiple mutations at the same time were needed for increased binding affinity towards human target protein, demonstrating that the probability of transmission to humans was extremely low when mutation rates were regarded. Still, further molecular studies are required to comprehensively conclude the possible transmission risk.

Keywords: Cyprus; coronaviruses; feline; in silico modeling.

Figure 1

Conserved domain analysis on members of alphacoronavirus. S1: S1 glycoprotein domain(pfam01600) of coronavirus, conserved TGEV-like_Spike_SD1-2_S1-S2_S2: domain (cd22377) located on C-terminal S1 region and S2 region of spike proteins, conserved HCoV/NL63/229E-like_Spike_SD1-2_S1-S2_S2domain (cl40439): located on C-terminal S1 region and S2 region of spike proteins, HR: heptad repeat, TM:transmembrane domain, CM: cysteine-rich C terminal intravirion (cl41189) motif, SP: signal Peptide, CS:cleavage site, and FP: fusion peptide. (A) FCoV-23, (B) FIPV, (C) FCoV-SB22 AND FCoV-UG-FH8, (D) PRCV, (E) TGEV, (F) HCoV-229E, and (G) HCoV-NL63.

Figure 2

Relationship between different alphacoronaviruses in terms of RBD region. (A) Multiple sequence alignment analysis and (B) schematic representation of phylogenetic analysis.

Figure 3

Primary structure-based interaction profiles of the proteins. Heat maps for the interaction of (A) FCoV-23 RBD-fAPN, (B) FCoV-23 RBD-hAPN, (C) HCoV-229E RBD-fAPN, and (D) HCoV-229E RBD-hAPN. Gray: The regions that are not involved in the interaction. Blue to red: Weak to strong interaction regions.