Molecular Basis of Hippopotamus ACE2 Binding to SARS-CoV-2

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2024 Apr 9

PMID 38591877

Authors

Ruirui Yang

Pu Han

Pengcheng Han

Dedong Li

Runchu Zhao

Sheng Niu

Kefang Liu

Shihua Li

Wen-Xia Tian

George Fu Gao

Affiliations

Soon will be listed here.

Abstract

Importance: The hippopotami are the first semi-aquatic artiodactyl mammals wherein SARS-CoV-2 infection has been reported. Exploration of the invasion mechanism of SARS-CoV-2 will provide important information for the surveillance of SARS-CoV-2 in hippopotami, as well as other semi-aquatic mammals and cetaceans. Here, we found that hippopotamus ACE2 (hiACE2) could efficiently bind to the RBDs of the SARS-CoV-2 prototype (PT) and variants of concern (VOCs) and facilitate the transduction of SARS-CoV-2 PT and VOCs pseudoviruses into hiACE2-expressing cells. The cryo-EM structure of the SARS-CoV-2 PT S protein complexed with hiACE2 elucidated a few critical residues in the RBD/hiACE2 interface, especially L30 and F83 of hiACE2 which are unique to hiACE2 and contributed to the decreased binding affinity to PT RBD compared to human ACE2. Our work provides insight into cross-species transmission and highlights the necessity for monitoring host jumps and spillover events on SARS-CoV-2 in semi-aquatic/aquatic mammals.

Citing Articles

Receptor binding and structural basis of raccoon dog ACE2 binding to SARS-CoV-2 prototype and its variants.

Luo C, Li L, Gu Y, Zhang H, Xu Z, Sun J PLoS Pathog. 2024; 20(12):e1012713.

PMID: 39637248 PMC: 11620640. DOI: 10.1371/journal.ppat.1012713.

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