Host range projection of SARS-CoV-2: South Asia perspective

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causing agent of Coronavirus Disease-2019 (COVID-19), is likely to be originated from bat and transmitted through intermediate hosts. However, the immediate source species of SARS-CoV-2 have not yet been confirmed. Here, we used diversity analysis of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2 and transmembrane protease serine 2 (TMPRSS2), which has been proved to be utilized by SARS-CoV-2 for spike protein priming. We also simulated the structure of receptor-binding domain of SARS-CoV-2 spike protein (SARS-CoV-2S RBD) with the ACE2s to investigate their binding affinity to determine the potential intermediate animal hosts that could spread the SARS-CoV-2 to humans in South Asia. We identified cow, buffalo, goat and sheep, which are predominant species in the household farming system in South Asia that can potentially be infected by SARS-CoV-2. All the bird species studied along with rat and mouse were considered less potential to interact with SARS-CoV-2. The interaction interfaces of SARS-CoV-2S RBD and ACE2 protein complex suggests pangolin as a potential intermediate host in SARS-CoV-2. Our results provide a valuable resource for the identification of potential hosts for SARS-CoV-2 in South Asia and henceforth reduce the opportunity for a future outbreak of COVID-19.

Keywords: ACE2; COVID-19; Host range; SARS-CoV-2; TMPRSS2.

Fig. 1

Phylogenetic analysis of protein sequences from the selected species. The trees were constructed on the whole aa sequences using maximum-likelihood method by MEGAX with 1000 bootstrap replicates. A, phylogenetic tree of ACE2 protein sequences of different species. B, phylogenetic tree of TMPRSS2 protein sequences of different species.

Fig. 2

Overall structure simulation and structural details at the binding interface of SARS-COV-2S RBD and human ACE2. HumanACE2 and SARS-COV-2 S RBD are in forest green and red, respectively.

Fig. 3

Comparisons of interactions at the SARS-CoV-2S RBD and ACE2 interfaces. A, simulation of structural details at the binding interface of SARS-COV-2 S RBD and PangolinACE2. PangolinACE2 and SARS-CoV-2S RBD are in deep skyblue and red, respectively. B, simulation of structural details at the binding interface of SARS-CoV-2S RBD and Intermediate horseshoe batACE2. Intermediate horseshoe batACE2 and SARS-CoV-2S RBD are in purple and red, respectively. C, simulation of structural details at the binding interface of SARS-CoV-2S RBD and CowACE2. CowACE2 and SARS-CoV-2S RBD are in dark khaki and red, respectively. D, simulation of structural details at the binding interface of SARS-CoV-2S RBD and GoatACE2. GoatACE2 and SARS-CoV-2S RBD are in goldenrod and red, respectively. E, simulation of structural details at the binding interface of SARS-CoV-2S RBD and CatACE2. CatACE2 and SARS-CoV-2S RBD are in dark cyan and red, respectively. F, simulation of structural details at the binding interface of SARS-CoV-2S RBD and DogACE2. DogACE2 and SARS-CoV-2S RBD are in dim gray and red, respectively.