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Title: Genetic variations affecting ACE2 protein stability in minority populations
While worldwide efforts for improving COVID-19 vaccines are currently considered a top priority, the role of the genetic variants responsible for virus receptor protein stability is less studied. Angiotensin-converting enzyme-2 is the primary target of the SARS-CoV-1/SARS-CoV-2 spike (S) glycoprotein, enabling entry into the human body. Here, we applied computational saturation mutagenesis approaches to determine the folding energy caused by all possible mutations in ACE2 proteins within ACE2 - SARS-CoV-1-S/ACE2 - SARS-CoV-2-S complexes. We observed ACE2 mutations at residue D350 causing the most stabilizing effects on the protein. In addition, we identified ACE2 genetic variations in African Americans (rs73635825, rs766996587, and rs780574871), Latino Americans (rs924799658), and both groups (rs4646116 and rs138390800) affecting stability in the ACE2 - SARS-CoV-2-S complex. The findings in this study may aid in targeting the design of stable neutralizing peptides for treating minority patients.  more » « less
Award ID(s):
1924092
PAR ID:
10481318
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Publisher / Repository:
Frontiers
Date Published:
Journal Name:
Frontiers in Medicine
Volume:
9
ISSN:
2296-858X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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