Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C1175175 (
SARS
)
19,188
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Current
SARS
-CoV-2 pandemy mortality created the hypothesis that some populations may be more susceptible to
SARS
-CoV-2.
TMPRSS2
encodes a transmembrane serine protease which plays a crucial role in
SARS
-CoV-2 cell entry. Single nucleotide polymorphisms (SNPs) in
TMPRSS2
might influence
SARS
-CoV2 entry into the cell. This study aimed to investigate the impact of SNPs on TMPRSS2 function and structure.
In silico
tools such as Ensembl, Gtex, ExPASY 2, GEPIA, CCLE, KEGG and GO were engaged to characterize
TMPRSS2
and its expression profile. The functional effects of SNPs were analyzed by PolyPhen-2, PROVEN, SNAP2, SIFT and HSF. Also, Phyre2,
GOR
IV and PSIPRED were used to predict the secondary structure of TMPRSS2. Moreover, post-translational modification (PTM) and secretory properties were analyzed through Modpredand Phobius, respectively. Finally, miRNA profiles were investigated by PolymiRTS and miRSNPs. Out of 11,184 retrieved SNPs from dbSNP, 92 showed a different frequency between Asians and other populations. Only 21 SNPs affected the function and structure of TMPRSS2 by influencing the protein folding, PTM, splicing and miRNA function. Particularly, rs12329760 may create a
de novo
pocket protein. rs875393 can create a donor site, silencer and broken enhancer motifs. rs12627374 affects a wide spectrum of miRNAs profile. This study highlighted the role of
TMPRSS2 SNPs
and epigenetic mechanisms especially non-coding RNAs in appearance of different susceptibility to
SARS
-CoV-2 among different populations. Also, this study could pave the way to potential therapeutic implication of TMPRSS2 in designing antiviral drugs.Communicated by Ramaswamy H. Sarma.
...
PMID:First comprehensive computational analysis of functional consequences of
TMPRSS2
SNPs in susceptibility to SARS-CoV-2 among different populations. 3241 May 2