Structural basis for bat receptor recognition by SARS-CoV-2 and bat SARS2-like coronaviruses

Area of Science:

• Virology
• Structural Biology
• Evolutionary Biology

Background:

• Coronaviruses adapt to bind host receptors effectively.
• The high affinity of SARS-CoV-2's receptor-binding domain (RBD) for human ACE2, despite limited adaptation time, remains a mystery.
• Some bat coronaviruses exhibit unusual binding affinities for human ACE2.

Purpose of the Study:

• To investigate the binding mechanisms of SARS-CoV-2 and a related bat coronavirus (BANAL-52) to ACE2 receptors.
• To compare the interactions of viral RBDs with bat and human ACE2.
• To understand the evolutionary origins of SARS-CoV-2's high affinity for human ACE2.

Main Methods:

• Comparative structural analysis of RBDs from SARS-CoV-2 and BANAL-52.
• Biochemical assays to quantify binding affinities between viral RBDs and ACE2 from Rhinolophus sinicus (RsBat) and humans.
• Detailed examination of key amino acid residues involved in receptor recognition.

Main Results:

• BANAL-52 RBD demonstrates strong binding to RsBat ACE2, facilitated by a favorable interaction between His498 (BANAL-52) and His41 (RsBat ACE2).
• SARS-CoV-2 RBD exhibits preferential binding to human ACE2, influenced by residues His34 and Met82 in human ACE2.
• These findings align with established principles of viral receptor recognition.

Conclusions:

• SARS-CoV-2's high affinity for human ACE2 is driven by specific interactions with human ACE2 residues.
• The binding patterns of SARS-CoV-2 and BANAL-52 are consistent with evolutionary adaptations for their respective hosts.
• This study provides crucial structural insights into the evolutionary trajectory leading to COVID-19.