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.
Subject(s)
Arthropod Proteins/metabolism , Arthropods/metabolism , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Arthropod Proteins/chemistry , Arthropod Proteins/genetics , Arthropods/chemistry , Arthropods/classification , Arthropods/genetics , Binding Sites , COVID-19/transmission , Ectoparasitic Infestations/parasitology , Humans , Models, Molecular , Mutation , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/genetics , Phylogeny , Protein Binding , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Sequence Homology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
Bacterial permeability family member A1 (BPIFA1) is one of the most abundant proteins present in normal airway surface liquid (ASL). It is known to be diminished in asthmatic patients' sputum, which causes airway hyperresponsiveness (AHR). What is currently unclear is how environmental factors, such as allergens' impact on BPIFA1's abundance and functions in the context of allergic asthma. House dust mite (HDM) is a predominant domestic source of aeroallergens. The group of proteases found in HDM is thought to cleave multiple cellular protective mechanisms, and therefore foster the development of allergic asthma. Here, we show that BPIFA1 is cleaved by HDM proteases in a time-, dose-, and temperature-dependent manner. We have also shown the main component in HDM that is responsible for BPIFA1's degradation is Der p1. Fragmented BPIFA1 failed to bind E. coli lipopolysaccharide (LPS), and hence elevated TNFα and IL-6 secretion in human whole blood. BPIFA1 degradation is also observed in vivo in bronchoalveolar fluid (BALF) of mice which are intranasally instilled with HDM. These data suggest that proteases associated with environmental allergens such as HDM cleave BPIFA1 and therefore impair its immune modulator function.