The molecular basis for SARS-CoV-2 binding to dog ACE2

Area of Science:

• Virology
• Molecular Biology
• Structural Biology

Background:

• SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has demonstrated the ability to infect a wide range of domestic animals.
• Understanding the molecular mechanisms of viral entry into animal hosts is crucial for controlling zoonotic diseases.

Purpose of the Study:

• To investigate the interaction between the SARS-CoV-2 spike protein receptor-binding domain (RBD) and dog angiotensin-converting enzyme 2 (dACE2).
• To elucidate the structural basis for SARS-CoV-2 binding to dACE2 and its implications for cross-species transmission.

Main Methods:

• Crystallography to determine the structure of the RBD-dACE2 complex.
• Infection assays using pseudotyped and authentic SARS-CoV-2 with dACE2-expressing cells.
• Analysis of binding interfaces and identification of key mutations.

Main Results:

• Dog ACE2 (dACE2) binds to the SARS-CoV-2 spike protein RBD.
• Both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells.
• The RBD-dACE2 complex has fewer contacts than the RBD-human ACE2 complex, indicating lower binding affinity.
• Specific mutations in the RBD binding interface significantly affect binding affinity to both dACE2 and human ACE2.

Conclusions:

• The study reveals the molecular basis for SARS-CoV-2 cross-species transmission into dogs.
• Identified mutations provide insights into viral binding affinity and potential targets for intervention.
• Findings contribute to understanding and blocking potential SARS-CoV-2 transmission chains involving domestic animals.