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Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26

Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and... Emerging Microbes & Infections 2020, VOL. 9 https://doi.org/10.1080/22221751.2020.1739565 Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26 Naveen Vankadari and Jacqueline A. Wilce Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia ABSTRACT The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with an increase in mortality and morbidity. Here we report our modelled homo-trimer structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which is involved in host cell adhesion. We also predict the unique N- and O-linked glycosylation sites of spike glycoprotein that distinguish it from the SARS and underlines shielding and camouflage of COVID-19 from the host the defence system. Furthermore, our study also highlights the key finding that the S1 domain of COVID-19 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence. These findings accentuate the unique features of COVID-19 and assist in the development of new therapeutics. ARTICLE HISTORY Received 4 February 2020; Revised 1 March 2020; Accepted 1 March 2020 KEYWORDS Coronavirus; CD26; glycosylation; DPP4; spike glycoprotein; docking An outbreak of potentially lethal coronavirus (named glycan shield pattern that has great implications for COVID-19) in Wuhan, China, is spreading globally understanding the viral camouflage and mode of cell and impacting millions of people geographically linked entry, potentially assisting the development of new vac- with the Chinese population [1]. Current evidence cines, antibodies, small-molecule drugs and screening suggests that the virus originated from wild animals of the human host targets. and birds (https://www.cdc.gov/coronavirus/)[2]. To The Clustal-W sequence alignment of COVID-19 date, more than 2,800 deaths and 87,000 confirmed and SARS-CoV spike glycoproteins (Figure S1) shows positive cases have been reported around the world, ∼91% identity in the S2 domain region (aa570– making COVID-19 a major health concern. As a first aa1278), however it lacks similarity in three regions line of treatment, along with the antiviral drugs, clini- (aa677–690, wing), (aa877–884 and aa930–943, stalk). cians are using SARS-CoV and MERS-CoV neutraliz- A larger sequence difference (∼55% identity), was ing antibodies targeting the S1 domain of the found in the S1 domain (aa01–aa550), which is known COVID-19 spike glycoprotein [1]. Very recently (25 for its host cell target interaction underlying cell January 2020) the first and complete genome sequence adhesion and virulence [4,5]. Despite sequence dissimi- of COVID-19 was deposited in the NCBI (GenBank: larity in the S1 domains there are conserved residues MN908947.3) providing the key to the likely structure involved in ternary folding which were conserved. and glycosylation pattern of the viral proteins and con- This suggests that the COVID-19 might interact with sequent mode of interaction with the host cell. Similar some of the previously known host targets (ACE2, to most other coronaviruses, the outer membrane spike CD26, Ezrin, cyclophilins), albeit via slightly varied mol- glycoprotein, known for its glycosylation [3], is the ecular interactions. Recent studies also support the prime host interacting protein with host cell targets possibility of COVID-19 and ACE-2 interaction [6]. (such as ACE2, CD26, Ezrin, cyclophilins and other To better understand the structure of COVID-19, cell adhesion factors) important for cell adhesion and including the position and orientation of unique resi- virulence [4,5]. However, the specific host cell factors dues involved in target binding, we modelled the or proteins that facilitate the novel COVID-19 remain homo-trimer structure of COVID-19 S1 and S2 elusive. The current study was thus undertaken to pre- domains (spike glycoprotein) using SWISS-MODEL dict the COVID-19 spike glycoprotein structure and (https://swissmodel.expasy.org/) using the structure of CONTACT Naveen Vankadari Naveen.vankadari@monash.edu Monash Biomedicine Discovery Institute and Department of Biochemistry and Mol- ecular Biology, Monash University, Clayton, VIC 3800, Australia Supplemental data for this article can be accessed https://doi.org/10.1080/22221751.2020.1739565 This article has been republished with minor changes. These changes do not impact the academic content of the article. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 602 N. Vankadari and J. A. Wilce Figure 1. Overall homo-trimer model structure of the COVID-19 spike glycoprotein (A) ligand unbound conformation (B) ligand- bound conformation. The three protomers are coloured pink, green and cyan. S1- and S2- domains labelled. Receptor-binding induced hinge motion of S1 is distinguishable. (C) Predicted Glycan shield (spheres) of COVID-19 (green) and SARS-CoV (blue) spike glycoproteins. predicted 3C-like proteinase cleavage site (yellow). Predicted N-linked glycosylation sites for COVID-19 (D) and SARS-CoV (E). Unique glycosylation sites are coloured in Blue, and shared sites are shaded in Red. SARS-CoV (PDB: 6ACD) [4]. This model was vali- homotrimer structure of COVID-19 in C3 symmetry dated using the C-Score (confidence score) and TM (Figure 1(A)) superimposes with SARS-CoV with a score (structural similarity) (Figure S2) demonstrating 0.85Å Cα RMSD and with a number of unique residues the most correct fold and confidence of the predicted exposed on the surface COVID-19. A second modelled structure. Further validation and refinement was com- structure of COVID-19 spike glycoprotein, in ligand- pleted by ensuring that the residues occupied Rama- bound conformation (Figure 1(B)) was also predicted chandran favoured positions using Coot (www.mrc- based on the SARS-CoV/ACE2 complex structure imb.cam.uk/) (Figure S2). All amino acid residues (PDB:6ACG) [4]. This shows S1 domains in an open were positioned according to their lowest energy poss- conformation, enabling it to interact with target host ible orientation in the final model. The final modelled proteins. As is the case for other coronaviruses [7], Emerging Microbes & Infections 603 Figure 2. (A and B) Ribbon and a surface diagram showing the docking interface of modelled COVID-19 (grey) and human CD26 (orange)(PDB: 4QZV) complex. Predicted key residues involved in the interaction are shown in sticks (CD26 residues are underlined) (C) Overall docking results showing the surface model of CD26 with COVID-19 predicted homo-trimer structure (ligand-bound conformation). we also identified 3C-like proteinase cleavage site or glycan camouflage pattern of the spike proteins, (TGRLQ^SLQTY) (aa 997–1007) in COVID-19 spike which may underlie differences in host immunity. glycoprotein using a server (https://services. This leads to the intriguing question of whether healthtech.dtu.dk/). This 3C-like proteinase cleavage COVID-19 could be responsive to a similar therapeutic site could represent a site for drug discovery as cur- approach to SARS [8]. rently being proposed for SARS-CoV [7]. Coronavirus trafficking into and hijacking the host To understand the glycosylation pattern and glycan cell is primarily driven by the N-terminal S1 domain shield of viral camouflage we used the (https://services. of spike glycoprotein that interacts with several host healthtech.dtu.dk/) and (http://glycam.org/) servers to cell proteins [4,5]. The host CD26 receptor cleaves predict N- and O-linked glycosylation sites on the sur- amino-terminal dipeptides from polypeptides with face of the modelled homo-trimer structure of COVID- either L-proline or L-alanine in the penultimate pos- 19 spike glycoprotein and verified them according to ition, leading to T-cell activation and thus acting as a their Solvent Accessible Surface Area (SASA) (Table key immunoregulatory factor in viral infections [9]. S1). The spike glycoprotein trimer was then subjected Considering the current public health crisis, we con- to a surface glycosylation builder (http://glycam.org/ sidered the potential molecular interactions between glycoprotien_builder/) for the predicted sites and visu- COVID-19 spike protein and human CD26, with an alized in PyMol. We also performed the same analysis interest to explore the structural differences or simi- for the SARS-CoV spike protein, to identify significant larities between SARS-CoV and COVID-19 spike differences in glycosylation patterns (Figure 1(D,E)). protein interactions. To this end, a computational The built glycosylation shield structures of COVID- model based selective docking was performed using 19 and SARS-CoV spike glycoproteins were superim- the server Cluspro protein–protein docking (Www.clu- posed and are shown in Figure 1(C). As shown in spro.bu.edu) and Frodock (http://frodock.chaconlab. Figure 1(C) and Table S1, there are a number of con- org/) for further validation using our modelled 3D served glycosylation sites between these two viral homotrimer structure of COVID-19 Spike glycoprotein strains, however there are also several unique glycosy- (Figure 2) and the human CD26 (PDB: 4QZV) [10]. The lation sites in COVID-19 compared to SARS-CoV binding free energies were taken into consideration for spike glycoprotein. This suggests a different shielding selecting the best possible model. The final rigid docked 604 N. Vankadari and J. A. Wilce complex structure was compared with the initial full- Funding length COVID-19 spike glycoprotein and CD26 and This work was supported by the National Health and Medi- their overall RMSD’s were found to be 1.34 and cal Research Council of Australia with grant APP1161916 0.28 Å for Cα atoms, respectively. awarded to J.A.W. The docked complex model of COVID-19 spike glycoprotein and CD26 (Figure 2)shows alarge ORCID interface between the proteins. This suggests a poss- ible tight interaction between the S1 domain loops Naveen Vankadari http://orcid.org/0000-0001-9363-080X Jacqueline A. Wilce http://orcid.org/0000-0002-8344-2626 in the modelled structure and the CD26 surface. Pre- vious studies of CD26 binding have shown that resi- dues K267, T288, A289, A291, L294, I295, R317, References Y322 and D542 interact with Bat-CoV (MERS) [1] Huang C, Wang Y, Li X, et al. Clinical features of spike protein [10]. Interestingly our docked model patients infected with 2019 novel coronavirus in supports this despite the variability between these Wuhan, China. Lancet. 2020;395(10223):497–506. spike proteins’ S1 domains, with the same CD26 resi- [2] Lu H, Stratton CW, Tang YW. Outbreak of pneumonia dues in close proximity to the active region of S1 of unknown etiology in Wuhan China: the mystery and domain in COVID-19. We also observed additional the miracle. J Med Virol. 2020;92(4):401–402. [3] Xiong XL, Tortorici MA, Snijder J, et al. Glycan shield residues (Q286, I287, N338, V341, R336) of CD26 and fusion activation of a deltacoronavirus spike glyco- predicted to interact with the S1 domain of the protein fine-tuned for enteric infections. J Virol. spikeprotein viavan derWaalsorbyhydrogenbond- 2018;92(4):e01628–17. ing. However, regarding the COVID-19 spike glyco- [4] Song WF, Gui M, Wang X, et al. Cryo-EM structure of protein, we noticed many different and unique the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog. residues (R408, Q409, T445, V417, L461, D467, 2018;14(8):e1007236. S469, L491, N492, D493, Y 494, T497, T150, Y504) [5] Millet JK, Kien F, Cheung C-Y, et al. Ezrin interacts predicted to interact with CD26. Some of these with the SARS coronavirus spike protein and restrains unique residues of S1 domain are also predicted infection at the entry stage. Plos One. 2012;7(11): interact with the ACE2 protein [6]. This underlines e49566. the novelty and uniqueness of COVID-19 and its [6] Xu X, Chen P, Wang J, et al. Evolution of the novel cor- onavirus from the ongoing Wuhan outbreak and mod- interaction with human target proteins. This obser- eling of its spike protein for risk of human vation guides us to suggest that COVID-19 may transmission. SCIENCE CHINA Life Sciences; share infection modes with that of SARS-CoV and 2020;63(3):457–460. MERS-CoV and that interactions with other targets [7] Grum-Tokars V, Ratia K, Begaye A, et al. Evaluating also warrant investigation. the 3C-like protease activity of SARS-coronavirus: rec- ommendations for standardized assays for drug dis- covery. Virus Res. 2008;133(1):63–73. Acknowledgements [8] Watanabe Y, Bowden TA, Wilson IA, et al. Exploitation of glycosylation in enveloped virus patho- We thank the Monash University Software Platform for biology. Biochim Biophys Acta Gen Subj. 2019;1863 licence access to the concerned software. I also acknowledge (10):1480–1497. Joseph Polidano of Monash University for editing and proof [9] Morimoto C, Schlossman SF. The structure and func- reading the manuscript. tion of CD26 in the T-cell immune response. Immunol Rev. 1998;161:55–70. [10] Wang Q, Qi J, Yuan Y, et al. Bat origins of MERS-CoV Disclosure statement supported by bat coronavirus HKU4 usage of human No potential conflict of interest was reported by the receptor CD26. Cell Host Microbe. 2014;16(3):328– author(s). 337. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Emerging Microbes and Infections Taylor & Francis

Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26

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Taylor & Francis
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© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd
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2222-1751
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10.1080/22221751.2020.1739565
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Abstract

Emerging Microbes & Infections 2020, VOL. 9 https://doi.org/10.1080/22221751.2020.1739565 Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26 Naveen Vankadari and Jacqueline A. Wilce Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia ABSTRACT The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with an increase in mortality and morbidity. Here we report our modelled homo-trimer structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which is involved in host cell adhesion. We also predict the unique N- and O-linked glycosylation sites of spike glycoprotein that distinguish it from the SARS and underlines shielding and camouflage of COVID-19 from the host the defence system. Furthermore, our study also highlights the key finding that the S1 domain of COVID-19 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence. These findings accentuate the unique features of COVID-19 and assist in the development of new therapeutics. ARTICLE HISTORY Received 4 February 2020; Revised 1 March 2020; Accepted 1 March 2020 KEYWORDS Coronavirus; CD26; glycosylation; DPP4; spike glycoprotein; docking An outbreak of potentially lethal coronavirus (named glycan shield pattern that has great implications for COVID-19) in Wuhan, China, is spreading globally understanding the viral camouflage and mode of cell and impacting millions of people geographically linked entry, potentially assisting the development of new vac- with the Chinese population [1]. Current evidence cines, antibodies, small-molecule drugs and screening suggests that the virus originated from wild animals of the human host targets. and birds (https://www.cdc.gov/coronavirus/)[2]. To The Clustal-W sequence alignment of COVID-19 date, more than 2,800 deaths and 87,000 confirmed and SARS-CoV spike glycoproteins (Figure S1) shows positive cases have been reported around the world, ∼91% identity in the S2 domain region (aa570– making COVID-19 a major health concern. As a first aa1278), however it lacks similarity in three regions line of treatment, along with the antiviral drugs, clini- (aa677–690, wing), (aa877–884 and aa930–943, stalk). cians are using SARS-CoV and MERS-CoV neutraliz- A larger sequence difference (∼55% identity), was ing antibodies targeting the S1 domain of the found in the S1 domain (aa01–aa550), which is known COVID-19 spike glycoprotein [1]. Very recently (25 for its host cell target interaction underlying cell January 2020) the first and complete genome sequence adhesion and virulence [4,5]. Despite sequence dissimi- of COVID-19 was deposited in the NCBI (GenBank: larity in the S1 domains there are conserved residues MN908947.3) providing the key to the likely structure involved in ternary folding which were conserved. and glycosylation pattern of the viral proteins and con- This suggests that the COVID-19 might interact with sequent mode of interaction with the host cell. Similar some of the previously known host targets (ACE2, to most other coronaviruses, the outer membrane spike CD26, Ezrin, cyclophilins), albeit via slightly varied mol- glycoprotein, known for its glycosylation [3], is the ecular interactions. Recent studies also support the prime host interacting protein with host cell targets possibility of COVID-19 and ACE-2 interaction [6]. (such as ACE2, CD26, Ezrin, cyclophilins and other To better understand the structure of COVID-19, cell adhesion factors) important for cell adhesion and including the position and orientation of unique resi- virulence [4,5]. However, the specific host cell factors dues involved in target binding, we modelled the or proteins that facilitate the novel COVID-19 remain homo-trimer structure of COVID-19 S1 and S2 elusive. The current study was thus undertaken to pre- domains (spike glycoprotein) using SWISS-MODEL dict the COVID-19 spike glycoprotein structure and (https://swissmodel.expasy.org/) using the structure of CONTACT Naveen Vankadari Naveen.vankadari@monash.edu Monash Biomedicine Discovery Institute and Department of Biochemistry and Mol- ecular Biology, Monash University, Clayton, VIC 3800, Australia Supplemental data for this article can be accessed https://doi.org/10.1080/22221751.2020.1739565 This article has been republished with minor changes. These changes do not impact the academic content of the article. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 602 N. Vankadari and J. A. Wilce Figure 1. Overall homo-trimer model structure of the COVID-19 spike glycoprotein (A) ligand unbound conformation (B) ligand- bound conformation. The three protomers are coloured pink, green and cyan. S1- and S2- domains labelled. Receptor-binding induced hinge motion of S1 is distinguishable. (C) Predicted Glycan shield (spheres) of COVID-19 (green) and SARS-CoV (blue) spike glycoproteins. predicted 3C-like proteinase cleavage site (yellow). Predicted N-linked glycosylation sites for COVID-19 (D) and SARS-CoV (E). Unique glycosylation sites are coloured in Blue, and shared sites are shaded in Red. SARS-CoV (PDB: 6ACD) [4]. This model was vali- homotrimer structure of COVID-19 in C3 symmetry dated using the C-Score (confidence score) and TM (Figure 1(A)) superimposes with SARS-CoV with a score (structural similarity) (Figure S2) demonstrating 0.85Å Cα RMSD and with a number of unique residues the most correct fold and confidence of the predicted exposed on the surface COVID-19. A second modelled structure. Further validation and refinement was com- structure of COVID-19 spike glycoprotein, in ligand- pleted by ensuring that the residues occupied Rama- bound conformation (Figure 1(B)) was also predicted chandran favoured positions using Coot (www.mrc- based on the SARS-CoV/ACE2 complex structure imb.cam.uk/) (Figure S2). All amino acid residues (PDB:6ACG) [4]. This shows S1 domains in an open were positioned according to their lowest energy poss- conformation, enabling it to interact with target host ible orientation in the final model. The final modelled proteins. As is the case for other coronaviruses [7], Emerging Microbes & Infections 603 Figure 2. (A and B) Ribbon and a surface diagram showing the docking interface of modelled COVID-19 (grey) and human CD26 (orange)(PDB: 4QZV) complex. Predicted key residues involved in the interaction are shown in sticks (CD26 residues are underlined) (C) Overall docking results showing the surface model of CD26 with COVID-19 predicted homo-trimer structure (ligand-bound conformation). we also identified 3C-like proteinase cleavage site or glycan camouflage pattern of the spike proteins, (TGRLQ^SLQTY) (aa 997–1007) in COVID-19 spike which may underlie differences in host immunity. glycoprotein using a server (https://services. This leads to the intriguing question of whether healthtech.dtu.dk/). This 3C-like proteinase cleavage COVID-19 could be responsive to a similar therapeutic site could represent a site for drug discovery as cur- approach to SARS [8]. rently being proposed for SARS-CoV [7]. Coronavirus trafficking into and hijacking the host To understand the glycosylation pattern and glycan cell is primarily driven by the N-terminal S1 domain shield of viral camouflage we used the (https://services. of spike glycoprotein that interacts with several host healthtech.dtu.dk/) and (http://glycam.org/) servers to cell proteins [4,5]. The host CD26 receptor cleaves predict N- and O-linked glycosylation sites on the sur- amino-terminal dipeptides from polypeptides with face of the modelled homo-trimer structure of COVID- either L-proline or L-alanine in the penultimate pos- 19 spike glycoprotein and verified them according to ition, leading to T-cell activation and thus acting as a their Solvent Accessible Surface Area (SASA) (Table key immunoregulatory factor in viral infections [9]. S1). The spike glycoprotein trimer was then subjected Considering the current public health crisis, we con- to a surface glycosylation builder (http://glycam.org/ sidered the potential molecular interactions between glycoprotien_builder/) for the predicted sites and visu- COVID-19 spike protein and human CD26, with an alized in PyMol. We also performed the same analysis interest to explore the structural differences or simi- for the SARS-CoV spike protein, to identify significant larities between SARS-CoV and COVID-19 spike differences in glycosylation patterns (Figure 1(D,E)). protein interactions. To this end, a computational The built glycosylation shield structures of COVID- model based selective docking was performed using 19 and SARS-CoV spike glycoproteins were superim- the server Cluspro protein–protein docking (Www.clu- posed and are shown in Figure 1(C). As shown in spro.bu.edu) and Frodock (http://frodock.chaconlab. Figure 1(C) and Table S1, there are a number of con- org/) for further validation using our modelled 3D served glycosylation sites between these two viral homotrimer structure of COVID-19 Spike glycoprotein strains, however there are also several unique glycosy- (Figure 2) and the human CD26 (PDB: 4QZV) [10]. The lation sites in COVID-19 compared to SARS-CoV binding free energies were taken into consideration for spike glycoprotein. This suggests a different shielding selecting the best possible model. The final rigid docked 604 N. Vankadari and J. A. Wilce complex structure was compared with the initial full- Funding length COVID-19 spike glycoprotein and CD26 and This work was supported by the National Health and Medi- their overall RMSD’s were found to be 1.34 and cal Research Council of Australia with grant APP1161916 0.28 Å for Cα atoms, respectively. awarded to J.A.W. The docked complex model of COVID-19 spike glycoprotein and CD26 (Figure 2)shows alarge ORCID interface between the proteins. This suggests a poss- ible tight interaction between the S1 domain loops Naveen Vankadari http://orcid.org/0000-0001-9363-080X Jacqueline A. Wilce http://orcid.org/0000-0002-8344-2626 in the modelled structure and the CD26 surface. Pre- vious studies of CD26 binding have shown that resi- dues K267, T288, A289, A291, L294, I295, R317, References Y322 and D542 interact with Bat-CoV (MERS) [1] Huang C, Wang Y, Li X, et al. Clinical features of spike protein [10]. Interestingly our docked model patients infected with 2019 novel coronavirus in supports this despite the variability between these Wuhan, China. Lancet. 2020;395(10223):497–506. spike proteins’ S1 domains, with the same CD26 resi- [2] Lu H, Stratton CW, Tang YW. Outbreak of pneumonia dues in close proximity to the active region of S1 of unknown etiology in Wuhan China: the mystery and domain in COVID-19. We also observed additional the miracle. J Med Virol. 2020;92(4):401–402. [3] Xiong XL, Tortorici MA, Snijder J, et al. Glycan shield residues (Q286, I287, N338, V341, R336) of CD26 and fusion activation of a deltacoronavirus spike glyco- predicted to interact with the S1 domain of the protein fine-tuned for enteric infections. J Virol. spikeprotein viavan derWaalsorbyhydrogenbond- 2018;92(4):e01628–17. ing. However, regarding the COVID-19 spike glyco- [4] Song WF, Gui M, Wang X, et al. Cryo-EM structure of protein, we noticed many different and unique the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog. residues (R408, Q409, T445, V417, L461, D467, 2018;14(8):e1007236. S469, L491, N492, D493, Y 494, T497, T150, Y504) [5] Millet JK, Kien F, Cheung C-Y, et al. Ezrin interacts predicted to interact with CD26. Some of these with the SARS coronavirus spike protein and restrains unique residues of S1 domain are also predicted infection at the entry stage. Plos One. 2012;7(11): interact with the ACE2 protein [6]. This underlines e49566. the novelty and uniqueness of COVID-19 and its [6] Xu X, Chen P, Wang J, et al. Evolution of the novel cor- onavirus from the ongoing Wuhan outbreak and mod- interaction with human target proteins. This obser- eling of its spike protein for risk of human vation guides us to suggest that COVID-19 may transmission. SCIENCE CHINA Life Sciences; share infection modes with that of SARS-CoV and 2020;63(3):457–460. MERS-CoV and that interactions with other targets [7] Grum-Tokars V, Ratia K, Begaye A, et al. Evaluating also warrant investigation. the 3C-like protease activity of SARS-coronavirus: rec- ommendations for standardized assays for drug dis- covery. Virus Res. 2008;133(1):63–73. Acknowledgements [8] Watanabe Y, Bowden TA, Wilson IA, et al. Exploitation of glycosylation in enveloped virus patho- We thank the Monash University Software Platform for biology. Biochim Biophys Acta Gen Subj. 2019;1863 licence access to the concerned software. I also acknowledge (10):1480–1497. Joseph Polidano of Monash University for editing and proof [9] Morimoto C, Schlossman SF. The structure and func- reading the manuscript. tion of CD26 in the T-cell immune response. Immunol Rev. 1998;161:55–70. [10] Wang Q, Qi J, Yuan Y, et al. Bat origins of MERS-CoV Disclosure statement supported by bat coronavirus HKU4 usage of human No potential conflict of interest was reported by the receptor CD26. Cell Host Microbe. 2014;16(3):328– author(s). 337.

Journal

Emerging Microbes and InfectionsTaylor & Francis

Published: Jan 1, 2020

Keywords: Coronavirus; CD26; glycosylation; DPP4; spike glycoprotein; docking

There are no references for this article.