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Comparative genetic analyses of Korean bat coronaviruses with SARS-CoV and the newly emerged SARS-CoV-2

  • Na, Eun-Jee (Laboratory of Veterinary Infectious Disease, College of Veterinary of Medicine, Jeonbuk National University) ;
  • Lee, Sook-Young (Laboratory of Veterinary Infectious Disease, College of Veterinary of Medicine, Jeonbuk National University) ;
  • Kim, Hak Jun (Department of Chemistry, Pukyong National University) ;
  • Oem, Jae-Ku (Laboratory of Veterinary Infectious Disease, College of Veterinary of Medicine, Jeonbuk National University)
  • Received : 2020.10.30
  • Accepted : 2020.12.15
  • Published : 2021.01.31

Abstract

Background: Bats have been considered natural reservoirs for several pathogenic human coronaviruses (CoVs) in the last two decades. Recently, a bat CoV was detected in the Republic of Korea; its entire genome was sequenced and reported to be genetically similar to that of the severe acute respiratory syndrome CoV (SARS-CoV). Objectives: The objective of this study was to compare the genetic sequences of SARS-CoV, SARS-CoV-2, and the two Korean bat CoV strains 16BO133 and B15-21, to estimate the likelihood of an interaction between the Korean bat CoVs and the human angiotensin-converting enzyme 2 (ACE2) receptor. Methods: The phylogenetic analysis was conducted with the maximum-likelihood (ML) method using MEGA 7 software. The Korean bat CoVs receptor binding domain (RBD) of the spike protein was analyzed by comparative homology modeling using the SWISS-MODEL server. The binding energies of the complexes were calculated using PRODIGY and MM/GBGA. Results: Phylogenetic analyses of the entire RNA-dependent RNA polymerase, spike regions, and the complete genome revealed that the Korean CoVs, along with SARS-CoV and SARS-CoV-2, belong to the subgenus Sarbecovirus, within BetaCoVs. However, the two Korean CoVs were distinct from SARS-CoV-2. Specifically, the spike gene of the Korean CoVs, which is involved in host infection, differed from that of SARS-CoV-2, showing only 66.8%-67.0% nucleotide homology and presented deletions within the RBD, particularly within regions critical for cross-species transmission and that mediate interaction with ACE2. Binding free energy calculation revealed that the binding affinity of Korean bat CoV RBD to hACE2 was drastically lower than that of SARS-CoV and SARS-CoV-2. Conclusions: These results suggest that Korean bat CoVs are unlikely to bind to the human ACE2 receptor.

Keywords

Acknowledgement

This research was supported by the "Research Base Construction Fund Support Program," funded by the Jeonbuk National University in 2020. This research was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2019R1A6A1A03033084). This study was partially supported by the National Research Foundation of Korea (Grant Number: NRF-2018R1D1A1B07041764).

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