Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry

doi:10.1080/22221751.2020.1770631

. 2020 Dec;9(1):1238-1241.

doi: 10.1080/22221751.2020.1770631.

Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry

Huan Sun¹, Yan Li¹, Peipei Liu², Chengpeng Qiao³, Xiaomin Wang^{1

4}, Lianao Wu^{1

5}, Kefang Liu¹, Yu Hu¹, Chao Su^{1

6}, Shuguang Tan¹, Shumei Zou², Guizhen Wu², Jinghua Yan^{1

3

7}, George Fu Gao¹, Jianxun Qi^{1

7}, Qihui Wang^{1

3}

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, People's Republic of China.
² NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
³ CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
⁴ University of Chinese Academy of Sciences, Beijing, People's Republic of China.
⁵ Institute of Physical Science and Information, Anhui University, Hefei, People's Republic of China.
⁶ College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
⁷ Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People's Republic of China.

PMID: 32482145
PMCID: PMC7448930
DOI: 10.1080/22221751.2020.1770631

Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry

Huan Sun et al. Emerg Microbes Infect. 2020 Dec.

. 2020 Dec;9(1):1238-1241.

doi: 10.1080/22221751.2020.1770631.

Authors

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, People's Republic of China.
² NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
³ CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
⁴ University of Chinese Academy of Sciences, Beijing, People's Republic of China.
⁵ Institute of Physical Science and Information, Anhui University, Hefei, People's Republic of China.
⁶ College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
⁷ Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People's Republic of China.

PMID: 32482145
PMCID: PMC7448930
DOI: 10.1080/22221751.2020.1770631

No abstract available

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

**Figure 1.**
Structure of fusion core of HCoV-19 and identification of an inhibitory peptide for virus fusion. (a) Schematic representation of the extracellular region of HCoV-19 spike protein (S). SP, signal peptide. NTD, N-terminal domain. RBD, receptor-binding domain. Sequence alignment between HCoV-19, RaTG13, ZC45, ZXC21, WIV16, SARS-CoV and MERS-CoV S proteins for the HR1 and HR2 regions is shown. (b) Overall structure of the HR1/HR2 complex. (c) Six-helix bundle fusion core structure yielded by symmetry operations. The three HR1/HR2 chains are colored lemon, cyan, and magenta, respectively. Structures in top view (left panel) and side view (right panel) are presented, respectively. (d) The detailed interactions between HR1 and HR2. Residues involved in the hydrogen bond interactions were shown as sticks and labeled. (e) Hydrophobicity map was presented on the left panel. The two contacted HR1/HR2 complexes were illustrated with ribbon representation. The right showed the hydrophobic residues constituting this hydrophobic surface. (f) Inhibitory activity of P1, P2, P3 and P4 peptides, which were derived from S protein, against HCoV-19 S mediated cell–cell fusion. EK1 peptide as the positive control. Experiments were performed twice, and the data are expressed as means ± SD (error bar) of one representative result. (g) Identification of inhibitory peptides derived from S protein with pseudotyped viruses. The percent inhibition (y-axis) was plotted against the log value of peptide concentration (x-axis), and the fusion inhibition curves are shown. Each point represented the mean + SD from triplicate experiments. The EC₅₀ values were listed. These results were representative data from two independent experiments. (h) Evaluation of P3 against live HCoV-19 infection. The relative ORF1ab RNA level of HCoV-19 (y-axis) was plotted against the log value of peptide concentration (x-axis). The amount of HCoV-19 in the samples was determined by RT-PCR. Values were means + SD of three samples per group. Experiments were performed twice and one representative data was displayed.

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References

1. Gao GF. From “A”IV to “Z”IKV: attacks from emerging and re-emerging pathogens. Cell. 2018;172(6):1157–1159. doi: 10.1016/j.cell.2018.02.025 - DOI - PMC - PubMed
1. Jiang S, Shi Z, Shu Y, et al. . A distinct name is needed for the new coronavirus. The Lancet. 2020;395(10228):949. doi: 10.1016/S0140-6736(20)30419-0 - DOI - PMC - PubMed
1. Lu G, Wang Q, Gao GF.. Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond. Trends Microbiol. 2015;23(8):468–478. doi: 10.1016/j.tim.2015.06.003 - DOI - PMC - PubMed
1. Gao J, Lu G, Qi J, et al. . Structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the S protein of middle east respiratory syndrome coronavirus. J Virol. 2013;87(24):13134–13140. doi: 10.1128/JVI.02433-13 - DOI - PMC - PubMed
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[1] Gao GF. From “A”IV to “Z”IKV: attacks from emerging and re-emerging pathogens. Cell. 2018;172(6):1157–1159. doi: 10.1016/j.cell.2018.02.025 - DOI - PMC - PubMed

[2] Gao GF. From “A”IV to “Z”IKV: attacks from emerging and re-emerging pathogens. Cell. 2018;172(6):1157–1159. doi: 10.1016/j.cell.2018.02.025 - DOI - PMC - PubMed

[3] Jiang S, Shi Z, Shu Y, et al. . A distinct name is needed for the new coronavirus. The Lancet. 2020;395(10228):949. doi: 10.1016/S0140-6736(20)30419-0 - DOI - PMC - PubMed

[4] Jiang S, Shi Z, Shu Y, et al. . A distinct name is needed for the new coronavirus. The Lancet. 2020;395(10228):949. doi: 10.1016/S0140-6736(20)30419-0 - DOI - PMC - PubMed

[5] Lu G, Wang Q, Gao GF.. Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond. Trends Microbiol. 2015;23(8):468–478. doi: 10.1016/j.tim.2015.06.003 - DOI - PMC - PubMed

[6] Lu G, Wang Q, Gao GF.. Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond. Trends Microbiol. 2015;23(8):468–478. doi: 10.1016/j.tim.2015.06.003 - DOI - PMC - PubMed

[7] Gao J, Lu G, Qi J, et al. . Structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the S protein of middle east respiratory syndrome coronavirus. J Virol. 2013;87(24):13134–13140. doi: 10.1128/JVI.02433-13 - DOI - PMC - PubMed

[8] Gao J, Lu G, Qi J, et al. . Structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the S protein of middle east respiratory syndrome coronavirus. J Virol. 2013;87(24):13134–13140. doi: 10.1128/JVI.02433-13 - DOI - PMC - PubMed

[9] Bosch BJ, Martina BE, Van Der Zee R, et al. . Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci USA. 2004;101(22):8455–8460. doi: 10.1073/pnas.0400576101 - DOI - PMC - PubMed

[10] Bosch BJ, Martina BE, Van Der Zee R, et al. . Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci USA. 2004;101(22):8455–8460. doi: 10.1073/pnas.0400576101 - DOI - PMC - PubMed

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Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry

Affiliations

Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry

Authors

Affiliations

Conflict of interest statement

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