Molecular evolution and phylogenetic analysis of SARS-CoV-2 and hosts ACE2 protein suggest Malayan pangolin as intermediary host

Braz J Microbiol. 2020 Dec;51(4):1593-1599. doi: 10.1007/s42770-020-00321-1. Epub 2020 Jun 26.

Abstract

An emergence of a novel coronavirus, causative agent of COVID19, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred due to cross-species transmission. Coronaviruses are a large family of viruses able to infect a great number of hosts. Entrance of SARS-CoV-2 depends on the surface (S) protein interaction with host ACE2 protein and cleavage by TMPRSS2. ACE2 could be a species-specific barrier that interferes with bat-to-human coronavirus cross-species transmission. Molecular analysis supported bats as natural hosts for SARS-CoV and involved them in MERS-CoV origin. The genomic similarity between bat RaTG13 CoV strain and SARS-CoV-2 implicates bats in the origin of the new outbreak. Additionally, there is a hypothesis for the zoonotic transmission based on contact with Malayan pangolins by humans in Huanan seafood market in Wuhan, China. To investigate bats and pangolin as hosts in SARS-CoV-2 cross-species transmission, we perform an evolutionary analysis combining viral and host phylogenies and divergence of ACE2 and TMPRSS2 amino acid sequences between CoV hosts. Phylogeny showed SARS-like-CoV-2 strains that infected pangolin and bats are close to SARS-CoV-2. In contrast to TMPRSS2, pangolin ACE2 amino acid sequence has low evolutionary divergence compared with humans and is more divergent from bats. Comparing SARS-CoV with SARS-CoV-2 origins, pangolin has yet lower ACE2 evolutionary divergence with humans than civet-the main intermediary host of SARS-CoV. Thus, pangolin has become an opportune host to intermediates bat-to-human SARS-CoV-2 jump and entry.

Keywords: ACE2; Bat; Coronavirus; Host; SARS-CoV; SARS-CoV-2.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics*
  • Animals
  • COVID-19 / transmission*
  • China
  • Chiroptera / genetics
  • Chiroptera / virology
  • Coronavirus / genetics
  • Disease Reservoirs / virology
  • Evolution, Molecular
  • Genome, Viral
  • Host Specificity
  • Humans
  • Pangolins / genetics
  • Pangolins / virology*
  • Phylogeny
  • SARS-CoV-2 / genetics
  • Serine Endopeptidases / genetics
  • Spike Glycoprotein, Coronavirus / genetics*

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human