Prediction of SARS-CoV-2 hosts among Brazilian mammals and new coronavirus transmission chain using evolutionary bioinformatics

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 are thought to transmit to humans via wild mammals, especially bats. However, evidence for direct bat-to-human transmission is lacking. Involvement of intermediate hosts is considered a reason for SARS-CoV-2 transmission to humans and emergence of outbreak. Large biodiversity is found in tropical territories, such as Brazil. On the similar line, this study aimed to predict potential coronavirus hosts among Brazilian wild mammals based on angiotensin-converting enzyme 2 (ACE2) sequences using evolutionary bioinformatics. Cougar, maned wolf, and bush dogs were predicted as potential hosts for coronavirus. These indigenous carnivores are philogenetically closer to the known SARS-CoV/SARS-CoV-2 hosts and presented low ACE2 divergence. A new coronavirus transmission chain was developed in which white-tailed deer, a susceptible SARS-CoV-2 host, have the central position. Cougar play an important role because of its low divergent ACE2 level in deer and humans. The discovery of these potential coronavirus hosts will be useful for epidemiological surveillance and discovery of interventions that can contribute to break the transmission chain.

Supplementary information: The online version contains supplementary material available at 10.1186/s44149-021-00020-w.

Keywords: Angiotensin-converting enzyme 2; Brazilian mammals; Coronavirus; SARS-CoV-2; White-tailed deer.

Fig. 1

Evolutionary analysis based on angiotensin-converting enzyme 2 (ACE2). a Phylogenetic tree included 34 amino acid sequences. The species in blue represent the known severe acute respiratory syndrome coronavirus (SARS-CoV)-2 hosts, the species in gray represent the known MERS-CoV host, and the species in red represent the known SARS-CoV hosts. The numbers in the phylogenetic tree represent the posterior probability that are the confidence values from each clade (the higher confidence is 1). Scale bar indicates the number of substitutions/site for the trees. b Bayesian phylogenetic tree was based on ACE2 protein. ACE2 protein sequences were aligned and used to infer the evolutionary divergence values, represented in the matrix heatmap. The heatmap color gradient represents the evolutionary divergence based on the number of amino acid substitutions/site from a pairwise comparison between sequences, from low (red) to high (blue). Evolutionary divergence analyses were conducted using the JTT matrix-based model. The heatmap were constructed using the Microsoft Excel™ software

Fig. 2

Heatmap matrix was based on four ACE2 binding regions that encompass the key residues enabling interactions with the SARS-CoV-2 S protein, detailed on Table 2 and Supplementary file 1. The ACE2 binding regions were concatened and used to infer the evolutionary divergence values, represented in the matrix heatmap. The evolutionary divergence values are available in the Supplementary Table 2. The heatmap color gradients represent the evolutionary divergence based on the number of amino acid substitutions/site from a pairwise comparison between sequences, from low (red) to high (blue). Evolutionary divergence analyses were conducted using the JTT matrix-based model. The heatmap were constructed using the Microsoft Excel™ software

Fig. 3

Diagram displaying the potential transmission chain of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 among humans and wild animals. Known SARS-CoV-2 hosts (horseshoe bat and pangolin), susceptible hosts confirmed by previous studies (white-tailed deer, mink, domestic cat, and zoo felines) and potential SARS-CoV-2 hosts (cougar, maned wolf and bush dog) predicted by bioinformatics analysis were included. (From left to right) Horseshoe bats (Rhinolophus genus), the main animal reservoir of SARS-CoV-2 (SARS-like-CoV) and Malayan pangolin, the SARS-CoV-2 intermediate host. White-tailed deer are susceptible to SARS-CoV-2 infection and are preyed by cougars, a potential SARS-CoV-2 host predicted by this study. SARS-CoV-2 may transmit from humans to cougars, considering that lions and tigers were infected by SARS-CoV-2 in the zoo. Maned Wolf, a potential SARS-CoV-2 host, can prey on other deer species. Bush dog is likely to prey on deer, but evidence is lacking. D. rotundus, a vampire bat, is a SARS-like-CoV host that can feed on white-tailed deer and other deer species. Moreover, D. rotundus could spread coronavirus to other bat species or even to cougar, maned wolf or bush dog, although there is no scientific confirmation