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

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

doi:10.3390/v11010056

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.

Highlights

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel human coronavirus (Figure 1A), emerged in Saudi Arabia in 2012 [1], rapidly spread wordwide, and caused continuous outbreaks with significant mortality and morbidity [2,3]
In the early 1990s, Jiang et al and Wild et al identified potent HIV-1 fusion inhibitory peptides derived from the HIV-1 gp41 CHR domain, SJ-2176 and DP-178 [34,35]
There have been numerous reports showing that peptides derived from the heptad repeat 2 (HR2) domain in the class I membrane fusion proteins of some enveloped viruses, such as respiratory syncytial virus (RSV) [36], paramyxoviruses simian virus 5 (SV5) [37], Nipah virus [38], and mouse hepatitis virus (MHV) [39], exhibit inhibitory activity against the corresponding viruses

Summary

Introduction

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel human coronavirus (Figure 1A), emerged in Saudi Arabia in 2012 [1], rapidly spread wordwide, and caused continuous outbreaks with significant mortality and morbidity [2,3]. MERS-CoV uses dipeptidyl peptidase-4 (DPP4, named CD26), a type-II transmembrane glycoprotein, as the cellular receptor to infect humans and cause severe respiratory disease and other severe complications, including renal failure and even multiorgan failure [4–8]. No licensed vaccines or effective therapeutics against MERS-CoV infection have been approved by the U.S Food and Drug Administration (FDA). This calls for the urgent development of effective therapeutics against MERS-CoV infection for clinical use. Similar to other coronaviruses [9], MERS-CoV is an enveloped positive-sense single-stranded

Methods

Results

Conclusion