The novel coronavirus SARS-CoV-2: From a zoonotic infection to coronavirus disease 2019

Abstract

The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.

Keywords: CoV; SARS-CoV-2; bat coronaviruses; intermediate host; phylogeny; zoonotic infection.

Figure 1

Phylogenetic analyses of the bat and other mammalian coronaviruses in regard to the SARS‐CoV‐2. Phylogenetic analysis of bat CoV strains obtained from different geographical localizations. Mostly, the dataset was composed from Asiatic strains including bat SARS‐like viral agents. The human SARS‐CoV‐2 Wuhan‐Hu‐1 strain was used to show the genetic distance between the zoonotic and human strains. In the tree, it is highlighted the possible interspecies jump between different bat CoVs. To explain better the cluster formation, the tree branches were grouped into three groups designated with roman numerals I‐III. Only complete genomes for tracing the phylogenetic history of bat CoV were used. The nucleotide substitution model used was GTR + F + I + G4 for tree reconstruction, which was chosen by the Bayesian information criterion statistic model, utilizing 10 000 ultrafast bootstrap replicates for statistical significance. Only values of above 99% were demonstrated on important tree branches. The phylogenetic tree was constructed using the IQ‐TREE software v.16.12, applying the maximum likelihood approach. F, frequency; G4, gamma distribution; GTR, generalized time‐reversible; I, invariant; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 2

Phylogenetic analysis of zoonotic CoV strain obtained from different geographical localizations and outbreaks. In this analysis, different kinds of animals were included that were probably commercialized in the Chinese markets (camels, civets, dogs, donkeys, horses, swine, rats, deer, and pangolins). The human isolate Wuhan‐Hu‐1 strain was used to show the genetic distance between the zoonotic and human strains. We used only complete genomes for tracing the phylogenetic history of zoonotic CoVs. The nucleotide substitution model used was GTR + F + I + G4 for tree reconstruction, which was chosen by the Bayesian information criterion statistic model, utilizing 10 000 ultrafast bootstrap replicates for statistical significance. Only values of above 99% were demonstrated on important tree branches. The phylogenetic tree was constructed using the IQ‐TREE software v.16.12, applying the maximum likelihood approach. CoV, coronavirus; F, frequency; G4, gamma distribution; GTR, generalized time‐reversible; I, invariant

Figure 3

Possible routes of SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 interspecies jumps and transmission to the human population due to genomic adaptations that help the virus in the invasion of subsequent species. The image accentuates the zoonotic circulation of the viral agents in bat populations with subsequent jumps to intermediate hosts and finally, due to anthropogenic factors, the viruses can be disseminated in the human population. CoV, coronavirus; MERS, Middle East respiratory syndrome; SARS, severe acute respiratory syndrome