IN-SILICO STUDY OF SPLICING VARIATIONS ON ANGIOTENSIN CONVERTING ENZYME 2 (ACE2) AND ITS EFFECTS ON INFECTION FROM SARS-COV-2

• Main Author: Fauzan, Ihsan
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/57942
• Institution: Institut Teknologi Bandung

The current COVID-19 pandemic has reached around 152 million active cases. COVID-19 (SARS-CoV-2) is known to have a very high rate of spread. SARS-CoV-2 infection can be influenced by several factors, one of which is genetics. Single Nucleotide Polymorphism (SNP) on the spike protein receptor (ACE2) is known to affect a person's susceptibility to SARS-CoV-2 infection. This can be seen from the difference in the affinity of the interaction with spike protein (ACE2) in SARS-CoV-2. In addition to SNPs, Alternative Splicing (AS) is also thought to have a correlation with the affinity value for interactions with the SARS-CoV-2 spike protein. The Alternative Splicing (AS) phenomenon can produce various kinds of protein expression variations with different protein isoform variants. So far, the difference in interaction affinity with the SARS-CoV-2 spike protein in AS has not been widely reported. Therefore, this study aimed to determine the protein isoform resulting from Alternative Splicing in the ACE2 gene and its effect on SARS-CoV-2 infection. Molecular Docking was used to determine the binding affinity between the two spike proteins with SARS-CoV-2. The 3D protein model of ACE2 isoforms obtained from the database (ensemble.org) was validated by evaluating the model quality of each ACE2 isoform. From the docking analysis carried out, it showed variations in the docking scores of 8 protein isoform variants. The protein variant ACE2_205 did not show any interaction with the SARS-CoV-2 spike protein. Variants ACE2_206 and ACE2_207 showed a lower docking score than the other variants. In addition, important residues in the interaction of each variant were also analyzed. Residues Q42 and A384 are residues on the ACE2 protein that appear in interactions in more than 2 variants. These results indicate the possibility that splicing variations can cause differences in a person's level of susceptibility to SARS-CoV-2 infection, especially in the ACE2_205 variant that cannot interact with the SARS-CoV-2 spike protein.