Screening coronavirus and human proteins for sialic acid binding sites using a docking approach

Chia-Wen Wang; Oscar K. Lee; Wolfgang B. Fischer; Chia-Wen Wang; Oscar K. Lee; Wolfgang B. Fischer

doi:10.3934/biophy.2021019

AIMS Biophysics

2021, Volume 8, Issue 3: 248-263. doi: 10.3934/biophy.2021019

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Screening coronavirus and human proteins for sialic acid binding sites using a docking approach

1.
Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan
2.
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3.
Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan

Received: 22 April 2021 Accepted: 20 June 2021 Published: 24 June 2021

The initial step of interaction of some pathogens with the host is driven by the interaction of glycoproteins of either side via endcaps of their glycans. These end caps consist of sialic acids or sugar molecules. Coronaviruses (CoVs), including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are found to use this route of interaction. The strength and spatial interactions on the single molecule level of sialic acids with either the spike (S) protein of SARS coronaviruses, or human angiotensin-converting enzyme 2 (ACE2) and furin are probed and compared to the binding modes of those sugar molecules which are present in glycans of glycoproteins. The protocol of using single molecules is seen as a simplified but effective mimic of the complex mode of interaction of the glycans. Averaged estimated binding energies from a docking approach result in preferential binding of the sialic acids to a specific binding site of the S protein of human coronavirus OC43 (HCoV-OC43). Furin is proposed to provide better binding sites for sialic acids than ACE2, albeit outweighed by sites for other sugar molecules. Absolute minimal estimated binding energies indicate weak binding affinities and are indifferent to the type of sugar molecules and the proteins. Neither the proposed best binding sites of the sialic acids nor those of the sugar molecules overlap with any of the cleavage sites at the S protein and the active sites of the human proteins.
- sialic acids,
- sugar molecules,
- spike protein,
- SARS-CoV-2,
- human receptor proteins,
- docking approach
Citation: Chia-Wen Wang, Oscar K. Lee, Wolfgang B. Fischer. Screening coronavirus and human proteins for sialic acid binding sites using a docking approach[J]. AIMS Biophysics, 2021, 8(3): 248-263. doi: 10.3934/biophy.2021019

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Abstract

The initial step of interaction of some pathogens with the host is driven by the interaction of glycoproteins of either side via endcaps of their glycans. These end caps consist of sialic acids or sugar molecules. Coronaviruses (CoVs), including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are found to use this route of interaction. The strength and spatial interactions on the single molecule level of sialic acids with either the spike (S) protein of SARS coronaviruses, or human angiotensin-converting enzyme 2 (ACE2) and furin are probed and compared to the binding modes of those sugar molecules which are present in glycans of glycoproteins. The protocol of using single molecules is seen as a simplified but effective mimic of the complex mode of interaction of the glycans. Averaged estimated binding energies from a docking approach result in preferential binding of the sialic acids to a specific binding site of the S protein of human coronavirus OC43 (HCoV-OC43). Furin is proposed to provide better binding sites for sialic acids than ACE2, albeit outweighed by sites for other sugar molecules. Absolute minimal estimated binding energies indicate weak binding affinities and are indifferent to the type of sugar molecules and the proteins. Neither the proposed best binding sites of the sialic acids nor those of the sugar molecules overlap with any of the cleavage sites at the S protein and the active sites of the human proteins.

Acknowledgments

WBF and OKL thank the Ministry of Science and Technology, Taiwan (MOST-107-2112-M-010-001-MY3 to WBF and MOST 109-2823-8-010-003-CV to OKL) for financial support. We are grateful to the National Center for High-performance Computing, Hsinchu, Taiwan, for computer time and facilities.

Conflicts of interest

The authors declare there is no conflict of interest.

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