Abstract:
Hepatitis C virus (HCV) is an utmost communal well-being problem globally.
Globally about 177.5 million individuals are tainted with HCV. Pakistan has
second largest load of HCV with a country wide prevalence of 4.8 %. About 17
million mortal are tainted with HCV in Pakistan. Documenting the genetics of
HCV has important implications for understanding disease severity as well in
therapeutics. In this insilico study we conducted functional analysis of non coding 5’ and 3’ untranslated regions (UTRs) sequence of various HCV
genotypes by multiple sequence alignment. Alongside we formulated and
compared the secondary structures of these UTRs in Hepatitis C virus (HCV)
of different regions and genotypes. RNA-RNA interaction was used to compare
5’ and 3’ non-coding UTRs with rest of coding viral genome using the most
prevalent HCV-3a as model. Secondary structures of both UTRs regions were
analyzed to confirm the structural stability and its involvement in self regulation of genes for survival and pathogenicity in the host. Lastly a
phylogenetic analysis was constructed to determine homology and origin of
HCV-3a virus in Pakistan. 5′ UTR sequence show high homology in Pakistan
HCV-2a to HCV-3a sequence. The secondary structures of 5’ and 3’ UTRs of
HCV-2a and HCV-3a of Pakistan showed significant structural differences and
varying degree of stabilities in comparison to other countries i.e. India, Egypt,
Us and Japan. In our study the 5’ UTR of HCV-3a Pakistan has less minimum
free energies as compare to 3’ UTR of same genotypes. The interaction of non coding 5′ and 3′ UTR with ORF of HCV-3a Pakistan strain show 6-7 binding
sites with low hybridization energies <-20 kcal/mol at core, E1, E2, NS2,
NS4A, NS4B and NS5A. Phylogenetic analysis show that 5′ UTR HCV-2a
Pakistan is closely related to US HCV-2a and 5′ UTR of HCV-3a Pakistan is
closely related to that of 5′UTR of HCV-3a of India
