tetano
Editor, Senior Moderator
Bioinform Biol Insights
. 2021 Oct 26;15:11779322211054684.
doi: 10.1177/11779322211054684. eCollection 2021.
Prediction of the Effects of Variants and Differential Expression of Key Host Genes ACE2, TMPRSS2, and FURIN in SARS-CoV-2 Pathogenesis: An In Silico Approach
Md Shahadat Hossain[SUP] 1 [/SUP], Mahafujul Islam Quadery Tonmoy[SUP] 1 [/SUP], Atqiya Fariha[SUP] 1 [/SUP], Md Sajedul Islam[SUP] 2 [/SUP], Arpita Singha Roy[SUP] 1 [/SUP], Md Nur Islam[SUP] 1 [/SUP], Kumkum Kar[SUP] 1 [/SUP], Mohammad Rahanur Alam[SUP] 3 [/SUP], Md Mizanur Rahaman[SUP] 4 [/SUP]
Affiliations
Abstract
A new strain of the beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is solely responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although several studies suggest that the spike protein of this virus interacts with the cell surface receptor, angiotensin-converting enzyme 2 (ACE2), and is subsequently cleaved by TMPRSS2 and FURIN to enter into the host cell, conclusive insight about the interaction pattern of the variants of these proteins is still lacking. Thus, in this study, we analyzed the functional conjugation among the spike protein, ACE2, TMPRSS2, and FURIN in viral pathogenesis as well as the effects of the mutations of the proteins through the implementation of several bioinformatics approaches. Analysis of the intermolecular interactions revealed that T27A (ACE2), G476S (receptor-binding domain [RBD] of the spike protein), C297T (TMPRSS2), and P812S (cleavage site for TMPRSS2) coding variants may render resistance in viral infection, whereas Q493L (RBD), S477I (RBD), P681R (cleavage site for FURIN), and P683W (cleavage site for FURIN) may lead to increase viral infection. Genotype-specific expression analysis predicted several genetic variants of ACE2 (rs2158082, rs2106806, rs4830971, and rs4830972), TMPRSS2 (rs458213, rs468444, rs4290734, and rs6517666), and FURIN (rs78164913 and rs79742014) that significantly alter their normal expression which might affect the viral spread. Furthermore, we also found that ACE2, TMPRSS2, and FURIN proteins are functionally co-related with each other, and several genes are highly co-expressed with them, which might be involved in viral pathogenesis. This study will thus help in future genomics and proteomics studies of SARS-CoV-2 and will provide an opportunity to understand the underlying molecular mechanism during SARS-CoV-2 pathogenesis.
Keywords: ACE2; FURIN; SARS-CoV-2; TMPRSS2; co-expression analysis; mutation analysis.
. 2021 Oct 26;15:11779322211054684.
doi: 10.1177/11779322211054684. eCollection 2021.
Prediction of the Effects of Variants and Differential Expression of Key Host Genes ACE2, TMPRSS2, and FURIN in SARS-CoV-2 Pathogenesis: An In Silico Approach
Md Shahadat Hossain[SUP] 1 [/SUP], Mahafujul Islam Quadery Tonmoy[SUP] 1 [/SUP], Atqiya Fariha[SUP] 1 [/SUP], Md Sajedul Islam[SUP] 2 [/SUP], Arpita Singha Roy[SUP] 1 [/SUP], Md Nur Islam[SUP] 1 [/SUP], Kumkum Kar[SUP] 1 [/SUP], Mohammad Rahanur Alam[SUP] 3 [/SUP], Md Mizanur Rahaman[SUP] 4 [/SUP]
Affiliations
- PMID: 34720581
- PMCID: PMC8554545
- DOI: 10.1177/11779322211054684
Abstract
A new strain of the beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is solely responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although several studies suggest that the spike protein of this virus interacts with the cell surface receptor, angiotensin-converting enzyme 2 (ACE2), and is subsequently cleaved by TMPRSS2 and FURIN to enter into the host cell, conclusive insight about the interaction pattern of the variants of these proteins is still lacking. Thus, in this study, we analyzed the functional conjugation among the spike protein, ACE2, TMPRSS2, and FURIN in viral pathogenesis as well as the effects of the mutations of the proteins through the implementation of several bioinformatics approaches. Analysis of the intermolecular interactions revealed that T27A (ACE2), G476S (receptor-binding domain [RBD] of the spike protein), C297T (TMPRSS2), and P812S (cleavage site for TMPRSS2) coding variants may render resistance in viral infection, whereas Q493L (RBD), S477I (RBD), P681R (cleavage site for FURIN), and P683W (cleavage site for FURIN) may lead to increase viral infection. Genotype-specific expression analysis predicted several genetic variants of ACE2 (rs2158082, rs2106806, rs4830971, and rs4830972), TMPRSS2 (rs458213, rs468444, rs4290734, and rs6517666), and FURIN (rs78164913 and rs79742014) that significantly alter their normal expression which might affect the viral spread. Furthermore, we also found that ACE2, TMPRSS2, and FURIN proteins are functionally co-related with each other, and several genes are highly co-expressed with them, which might be involved in viral pathogenesis. This study will thus help in future genomics and proteomics studies of SARS-CoV-2 and will provide an opportunity to understand the underlying molecular mechanism during SARS-CoV-2 pathogenesis.
Keywords: ACE2; FURIN; SARS-CoV-2; TMPRSS2; co-expression analysis; mutation analysis.