Identifying Primate ACE2 Variants That Confer Resistance to SARS-CoV-2

Area of Science:

• Virology
• Genetics
• Primate Biology

Background:

• SARS-CoV-2 utilizes the spike protein to bind human ACE2 for cell entry.
• Understanding ACE2 variants is crucial for determining SARS-CoV-2 susceptibility across species.

Purpose of the Study:

• To investigate the impact of ACE2 variants on SARS-CoV-2 binding affinity.
• To explore the evolutionary basis of SARS-CoV-2 susceptibility in primates.

Main Methods:

• Analysis of human ACE2 variants at spike protein binding sites.
• Experimental assays and protein structure analysis to assess binding affinity.
• Sequencing of ACE2 genes from various nonhuman primate species.

Main Results:

• Identified human ACE2 variants that disrupt, reduce, or enhance spike protein binding.
• Discovered four common ACE2 variants in New World monkeys, Philippine tarsiers, and prosimians that strongly reduce binding affinity.
• Observed variants in Old World monkeys and prosimians that increase binding affinity.

Conclusions:

• Human ACE2 variants influence SARS-CoV-2 binding affinity.
• New World monkeys, Philippine tarsiers, and ancestral primates likely possessed strong resistance to SARS-CoV-2.
• Apes and Old World monkeys exhibit susceptibility similar to most humans, highlighting diverse evolutionary responses to the virus.