RESUMEN
It is two years now but the world is still struggling against COVID-19 due to the havoc created by the SARS-CoV-2 virus and its multiple variants. Considering this perspective, in this work, we have hypothesized a new approach in order to identify potential regions in SARS-CoV-2 similar to the human miRNAs. Thus, they may have similar consequences as caused by the human miRNAs in human body. Therefore, the same way by which human miRNAs are inhibited can be applied for such potential regions of virus as well by administering drugs to the interacting human proteins. In this regard, the multiple sequence alignment technique Clustal Omega is used to align 2656 human miRNAs with the SARS-CoV-2 reference genome to identify the potential regions within the virus reference genome which have high similarities with the human miRNAs. The potential regions in virus genome are identified based on the highest number of nucleotide match, greater than or equal to 5 at a genomic position, for the aligned miRNAs. As a result, 38 potential SARS-CoV-2 regions are identified consisting of 249 human miRNAs. Among these 38 potential regions, some top regions belong to nucleocapsid, RdRp, helicase, and ORF8. To understand the biological significance of these potential regions, the targets of the human miRNAs are considered for KEGG pathways and protein–protein and drug–protein interaction analysis as the human miRNAs are similar to the potential regions of SARS-CoV-2. Significant pathways are found which lead to comorbidities. Subsequently, drugs like emodin, bicalutamide, vorinostat, etc. are identified that may be used for clinical trials.
RESUMEN
SARS-CoV-2 has a higher chance of progression in adults of any age with certain underlying health conditions or comorbidities like cancer, neurological diseases and in certain cases may even lead to death. Like other viruses, SARS-CoV-2 also interacts with host proteins to pave its entry into host cells. Therefore, to understand the behaviour of SARS-CoV-2 and design of effective antiviral drugs, host-virus protein-protein interactions (PPIs) can be very useful. In this regard, we have initially created a human-SARS-CoV-2 PPI database from existing works in the literature which has resulted in 7085 unique PPIs. Subsequently, we have identified at most 10 proteins with highest degrees viz. hub proteins from interacting human proteins for individual virus protein. The identification of these hub proteins is important as they are connected to most of the other human proteins. Consequently, when they get affected, the potential diseases are triggered in the corresponding pathways, thereby leading to comorbidities. Furthermore, the biological significance of the identified hub proteins is shown using KEGG pathway and GO enrichment analysis. KEGG pathway analysis is also essential for identifying the pathways leading to comorbidities. Among others, SARS-CoV-2 proteins viz. NSP2, NSP5, Envelope and ORF10 interacting with human hub proteins like COX4I1, COX5A, COX5B, NDUFS1, CANX, HSP90AA1 and TP53 lead to comorbidities. Such comorbidities are Alzheimer, Parkinson, Huntington, HTLV-1 infection, prostate cancer and viral carcinogenesis. Subsequently, using Enrichr tool possible repurposable drugs which target the human hub proteins are reported in this paper as well. Therefore, this work provides a consolidated study for human-SARS-CoV-2 protein interactions to understand the relationship between comorbidity and hub proteins so that it may pave the way for the development of anti-viral drugs.