Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4

Shuai Xia; Qiaoshuai Lan; Jing Pu; Cong Wang; Zezhong Liu; Wei Xu; Qian Wang; Huan Liu; Shibo Jiang; Lu Lu

doi:10.3390/v11010056

Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4

Viruses. 2019 Jan 14;11(1):56. doi: 10.3390/v11010056.

Authors

Shuai Xia¹, Qiaoshuai Lan², Jing Pu³, Cong Wang⁴, Zezhong Liu⁵, Wei Xu⁶, Qian Wang⁷, Huan Liu⁸, Shibo Jiang^{9

10}, Lu Lu¹¹

Affiliations

¹ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. 15111010053@fudan.edu.cn.
² Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. 18111010010@fudan.edu.cn.
³ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. 17111010015@fudan.edu.cn.
⁴ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. 16111010068@fudan.edu.cn.
⁵ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. 17111010065@fudan.edu.cn.
⁶ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. xuwei11@fudan.edu.cn.
⁷ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. wang_qian@fudan.edu.cn.
⁸ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. liuhuan@wh.iov.cn.
⁹ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. shibojiang@fudan.edu.cn.
¹⁰ Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA. shibojiang@fudan.edu.cn.
¹¹ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China. lul@fudan.edu.cn.

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability. Moreover, these peptides, particularly HKU4-HR2P2 and HKU4-HR2P3, exhibited potent inhibitory activity against MERS-CoV S-mediated cell⁻cell fusion and viral infection, suggesting that these HKU4 HR2-derived peptides could be candidates for futher development as antiviral agents against MERS-CoV infection.

Keywords: HKU4; MERS-CoV; cell–cell fusion; fusion inhibitor; peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chiroptera / virology*
Middle East Respiratory Syndrome Coronavirus / chemistry*
Peptides / chemistry*
Phylogeny
Protein Binding
Spike Glycoprotein, Coronavirus / chemistry*
Viral Fusion Proteins / chemistry*
Virus Internalization*

Substances

Peptides
Spike Glycoprotein, Coronavirus
Viral Fusion Proteins