Molecular Basis for Receptor Recognition and Broad Host Tropism for Merbecovirus MjHKU4r-CoV-1

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2024 Jun 14

PMID 38877169

Authors

Zhennan Zhao

Xin Li

Yan Chai

Zhifeng Liu

Qihui Wang

George F Gao

Affiliations

Soon will be listed here.

Abstract

A novel pangolin-origin MERS-like coronavirus (CoV), MjHKU4r-CoV-1, was recently identified. It is closely related to bat HKU4-CoV, and is infectious in human organs and transgenic mice. MjHKU4r-CoV-1 uses the dipeptidyl peptidase 4 (DPP4 or CD26) receptor for virus entry and has a broad host tropism. However, the molecular mechanism of its receptor binding and determinants of host range are not yet clear. Herein, we determine the structure of the MjHKU4r-CoV-1 spike (S) protein receptor-binding domain (RBD) complexed with human CD26 (hCD26) to reveal the basis for its receptor binding. Measuring binding capacity toward multiple animal receptors for MjHKU4r-CoV-1, mutagenesis analyses, and homology modeling highlight that residue sites 291, 292, 294, 295, 336, and 344 of CD26 are the crucial host range determinants for MjHKU4r-CoV-1. These results broaden our understanding of this potentially high-risk virus and will help us prepare for possible outbreaks in the future.

Citing Articles

Structural basis for human DPP4 receptor recognition by a pangolin MERS-like coronavirus.

Yang M, Li Z, Chen J, Li Y, Xu R, Wang M PLoS Pathog. 2024; 20(11):e1012695.

PMID: 39514585 PMC: 11578449. DOI: 10.1371/journal.ppat.1012695.

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