Dual-targeting strategy enables extremely potent and broad inhibition of emerging MERS-related coronaviruses

Cell Discovery, 26 August, 2025, DOI：https://doi.org/10.1038/s41421-025-00827-8

Dual-targeting strategy enables extremely potent and broad inhibition of emerging MERS-related coronaviruses

Fanke Jiao, Suya Jin, Qian Wang, Wei Xu, Xinling Wang, Fei Sun, Lu Lu, Shibo Jiang, Yun Zhu & Shuai Xia

Abstract

Recently, the receptors of several MERS-related coronaviruses (MERSr-CoVs), including MjHKU4r-CoV-1, NeoCoV, PDF-2180, MOW15-22, PnNL2018B, HKU5-CoV-1 and HKU5-CoV-2 (Fig. 1a), have been continuously identified. Compared with the prototypical MERS-CoV, these MERSr-CoVs exhibit substantial alterations in their spike (S) proteins, particularly within the receptor-binding domain (RBD) (Fig. 1b; Supplementary Fig. S1a, b). Remarkably, many MERSr-CoVs diverge from the canonical use of DPP4 as a receptor (Fig. 1a), a hallmark of Merbecoviruses, and instead show the capacity to utilize ACE2 for cell entry. For instance, two bat-derived MERSr-CoVs, NeoCoV and PDF-2180, have been shown to use bat ACE2 as their entry receptor and display broad non-bat mammal ACE2 recognition, thus potentially facilitating their cross-species transmission to humans in the future. Importantly, the receptor-binding modes of these viruses are structurally distinct from that of MERS-CoV or SARS-CoV-2, allowing them to substantially evade immune responses induced by previously developed vaccines. These findings highlight the urgent need to develop antiviral agents capable of counteracting a wide range of emerging MERSr-CoVs.

文章链接：https://www.nature.com/articles/s41421-025-00827-8