Molecular dynamic analyses of the interaction of SARS-CoV-1 or 2 variants with various angiotensin-converting enzyme-2 species

Abstract

The transmembrane glycoprotein angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS). It was shown to be the receptor of severe acute respiratory syndrome coronavirus 2 in the COVID-19 outbreak (SARS-COV-2). Furthermore, ACE2 aids in the transport of amino acids across the membrane. ACE2 is lost from the membrane, resulting in soluble ACE2 (sACE2). We aim to examine the structural conformation alterations between SARS-CoV-1 or 2 variants at various periods with ACE2 from various sources, particularly in the area where it interacts with the viral protein and the receptor. It is important to study the molecular dynamics of ACE2/SARS-COV RBD when the structure is available on the database. Here we analyzed the crystal structure of ACE2 from Human, Dog, Mus, Cat, and Bat ACE2 in complex with RBD from SARS-COV-1 and SARS-COV-2. The result shows, there is a variation in the type of residues, number of contact atoms and hydrogen bonds in ACE2 and RBD during the interaction interfaces. By using molecular dynamics simulation, we can measure RMSD, RMSF, SASA, Rg and the difference in the percentage of α helix and β strand. As bat ACE2 & SARS-CoV-2 RBD found to have a high amount of β strand compared to another structure complex, while hACE2 & SARS-CoV-1 RBD has fewer amounts of β strand. Our study provides a deep view of the structure which is available and a summary of many works around ACE2/SARS-CoV RBD interaction.

Communicated by Ramaswamy H. Sarma

Keywords:

• ACE2
• SARS-CoV-2
• molecular dynamics simulation
• RBD

Authors’ contribution

M.A wrote the main manuscript and run the MD; A.S.A, A.A.E, W.A.E, R.E, H.S.M, H.W.A, Y.A.M, M.E.A, P.K.M., R.K.M: prepared the Figures, Tables, references and finally reviewed the manuscript. All authors read and approved the final manuscript.

Acknowledgement

The authors extend their appreciation to the Researchers Supporting Project number (PNURSP2024R357), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. All authors are thankful to their respective institutions/affiliations for the support.

Disclosure statement

Ethics approval and consent to participate is Not applicable.

Data availability statement

All the data use here can be found in https://www.rcsb.org/

Additional information

Funding

The study was financially supported by the Researchers Supporting Project number (PNURSP2024R357), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.