Arthropod Ectoparasites Have Potential to Bind SARS-CoV-2 via ACE

Abstract

Coronavirus-like organisms have been previously identified in Arthropod ectoparasites (such as ticks and unfed cat flea). Yet, the question regarding the possible role of these arthropods as SARS-CoV-2 passive/biological transmission vectors is still poorly explored. In this study, we performed in silico structural and binding energy calculations to assess the risks associated with possible ectoparasite transmission. We found sufficient similarity between ectoparasite ACE and human ACE2 protein sequences to build good quality 3D-models of the SARS-CoV-2 Spike:ACE complex to assess the impacts of ectoparasite mutations on complex stability. For several species (e.g., water flea, deer tick, body louse), our analyses showed no significant destabilisation of the SARS-CoV-2 Spike:ACE complex, suggesting these species would bind the viral Spike protein. Our structural analyses also provide structural rationale for interactions between the viral Spike and the ectoparasite ACE proteins. Although we do not have experimental evidence of infection in these ectoparasites, the predicted stability of the complex suggests this is possible, raising concerns of a possible role in passive transmission of the virus to their human hosts.

Keywords: ACE2; COVID-19; SARS-CoV-2; parasite; spike protein; structural bioinformatics.

Figure 1

Comparison of LigPlot predicted bonding interactions for Wuhan-Hu-1 strain with human, water flea, body louse and deer tick. Corresponding residues in each species with key human interface hotspots (Hotspot 1, Hotspot 2) and the hydrophobic pocket are indicated if they are predicted to be involved in interface interactions. Novel ectoparasite H-bond residues also shown (pale orange boxes).

Figure 2

Structures of human and modelled ectoparasite SARS-CoV-2 S-protein: ACE complexes.

Figure 3

Comparison of LigPlot predicted bonding interactions for B.1.1.7 clade with human, water flea, body louse and deer tick. Corresponding residues in each species with key human interface hotspots (Hotspot 1, Hotspot 2) and the hydrophobic pocket are indicated if they are predicted to be involved in interface interactions. Novel ectoparasite H-bond residues also shown (orange boxes). In body louse, the ectoparasite-specific H-bond between Thr47 and Tyr501 is indicated as an equivalent to the important ‘Hotspot 2’ found in human spike:ACE2 interface.

Figure 4

Structures of N501Y mutant show increased H-bond stabilisation in body louse.

Figure 5

Phylogenetic tree of ectoparasite cytochrome oxidase subunit 1 (COI) nucleotide sequences. The phylogenetic tree was inferred according to the Maximum Likelihood method. Genetic distance was computed using General Time Reversible model and gamma distributed rate variation among sites (GTR + G).

Figure 6

Animal hosts for ectoparasites. These animal hosts may be in contact with humans in domestic, agricultural or zoological settings. Numbers represent the predicted change in binding energy (ΔΔG) of the S-protein:ACE2 [31]. Supporting references [80,81,82,83].

Figure 7

Proposed role of arthropod vectors in SARS-CoV-2 passive transmission. Using flea as a model, coronavirus passive transmission could occur via contact with SARS-CoV-2-contaminated substrates and surfaces. Fleas can feed on SARS-CoV-2-infected animal hosts and virus transmission to humans occurs via contaminated mouthparts, blood-meal regurgitation or inherited virus RNA. Similar to RNAi mechanisms, virus RNA may be also transmitted transovarially and transstadially. Reverse zoonotic SARS-CoV-2 transmission may also occur with arthropod passive vectors.