Genetic variations affecting ACE2 protein stability in minority populations.

Autor:	Mahase V; Department of Biology, Howard University, Washington, DC, United States., Sobitan A; Department of Biology, Howard University, Washington, DC, United States., Rhoades R; Department of Biology, Howard University, Washington, DC, United States., Zhang F; Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China., Baranova A; School of Systems Biology, George Mason University, Manassas, VA, United States.; Research Centre for Medical Genetics, Moscow, Russia., Johnson M; Department of Community and Family Medicine, Howard University, Washington, DC, United States., Otolorin A; Department of Community and Family Medicine, Howard University, Washington, DC, United States., Tang Q; Department of Microbiology, Howard University College of Medicine, Washington, DC, United States., Teng S; Department of Biology, Howard University, Washington, DC, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2022 Oct 31; Vol. 9, pp. 1002187. Date of Electronic Publication: 2022 Oct 31 (Print Publication: 2022).
DOI:	10.3389/fmed.2022.1002187
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Mahase, Sobitan, Rhoades, Zhang, Baranova, Johnson, Otolorin, Tang and Teng.)
Databáze:	MEDLINE
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