Global surveillance and countermeasures for ACE2-using MERS-related coronaviruses with spillover risk

Area of Science:

• Virology
• Infectious Diseases
• Molecular Biology

Background:

• Middle East Respiratory Syndrome-related coronaviruses (MERSr-CoVs) typically use dipeptidyl peptidase 4 (DPP4) for cell entry.
• Understanding viral entry mechanisms is crucial for predicting and preventing zoonotic spillover.

Purpose of the Study:

• To investigate the cell entry mechanisms of MERSr-CoVs.
• To identify alternative receptors used by MERSr-CoVs for host cell invasion.

Main Methods:

• Comparative analysis of MERSr-CoVs' interaction with different cellular receptors.
• Viral entry assays using cell lines expressing ACE2 and DPP4.

Main Results:

• Three distinct MERSr-CoVs were identified that utilize the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry.
• These viruses do not depend on the canonical DPP4 receptor, challenging previous assumptions about MERSr-CoV tropism.
• ACE2-dependent MERSr-CoVs demonstrated efficient cell entry, suggesting potential for human transmission.

Conclusions:

• The discovery of ACE2-dependent MERSr-CoVs expands the known receptor usage for this virus family.
• These findings highlight a significant zoonotic risk, as ACE2 is the receptor for SARS-CoV-2.
• Urgent global surveillance and development of countermeasures are necessary to mitigate the threat of these novel MERSr-CoVs.