Inhibition of hepatitis C virus genotype 4 replication using siRNA targeted to the viral core region and the CD81 cellular receptor

Aljowaie, Reem M.; Almajhdi, Fahad N.; Ali, Hebatallh H; El-Wetidy, Mohammad S.; Shier, Medhat K.

doi:10.1007/s12192-020-01077-1

Cited by 7 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the HCV clinical diagnostic parameters (quantitative variables) were found non-significant between GT 1 and 4 patients, however; SGPT levels were noted statistically significant in GT 1 patients. It is evident from the previous studies that GT 1 induced hepatic co-morbidities (e.g., fibrosis, steatosis, and cirrhosis) are much severe, and more elevated hepatic enzymes profile (i.e., LFT) have been reported in infected patients ( Shier et al, 2014 , Shier et al, 2017 , Aljowaie et al, 2020 ). Another variable was the platelet count, which was found relatively low in HCV GT-1 patients, but it was associated with some patient’s medication history of administering antiplatelet agents (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…HCV non-structural proteins NS3/4A serine protease inhibitors), and with limited response to sofosbuvir (i.e. HCV non-structural protein NS5B; RdRp inhibitors)) (Petruzziello et al, 2016; Aljowaie et al, 2020 ). Furthermore, GT-3 infected populations are associated with an increased risk of accelerated liver disease progression ( McPhee, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…For such difficult-to-treat patients, next-generation DAAs (e.g., sofosbuvir/velpatasvir/voxilaprevir; glecaprevir/pibrentasvir) with promising clinical trial efficacies and an excellent treatment outcome in real-world clinical experiences are recommended ( McPhee, 2019 ). For HCV GT-4 in Egypt, Sustained virologic response rates (SVR; HCV viral load undetectable after the post completion of 12 weeks therapy) were achieved only 40–60% in patients administered to pegylated interferon plus ribavirin (PEG-IFN/RBV) ( Aljowaie et al, 2020 ). Furthermore, some studies also explored the increased risk of hepatocellular carcinoma directly associated with subtype 4o in infected individuals ( Aljowaie et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…For HCV GT-4 in Egypt, Sustained virologic response rates (SVR; HCV viral load undetectable after the post completion of 12 weeks therapy) were achieved only 40–60% in patients administered to pegylated interferon plus ribavirin (PEG-IFN/RBV) ( Aljowaie et al, 2020 ). Furthermore, some studies also explored the increased risk of hepatocellular carcinoma directly associated with subtype 4o in infected individuals ( Aljowaie et al, 2020 ). However; HCV rapid-diagnostic testing campaign is underway in Egypt and HCV positive patents are administered to newer IFN-free DAAs to cure the infection.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Almalki

Shahid

Abdalla

et al. 2021

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

Hepatitis C virus (HCV) subtypes are pre-requisite to predict endemicity, epidemiology, clinical pathogenesis, diagnosis, and treatment of chronic hepatitis C infection. HCV genotypes 4 and 1 are the most prevalent in Saudi Arabia, however; less consensus data exist on circulating HCV subtypes in infected individuals. This study was aimed to demonstrate the virological surveillance, phylogenetic analysis, and evolutionary relationship of HCV genotypes 4 and 1 subtypes in the Saudi population with the rest of the world. Fifty-five clinical specimens from different parts of the country were analyzed based on 5′ untranslated region (5′ UTR) amplification, direct sequencing, and for molecular evolutionary genetic analysis. Pair-wise comparison and multiple sequence alignment were performed to determine the nucleotide conservation, nucleotide variation, and positional mutations within the sequenced isolates. The evolutionary relationship of sequenced HCV isolates with referenced HCV strains from the rest of the world was established by computing pairwise genetic distances and generating phylogenetic trees. Twelve new sequences were submitted to GenBank, NCBI database. The results revealed that HCV subtype 4a is more prevalent preceded by 1a in the Saudi population. Molecular phylogeny predicts the descendants’ relationship of subtype 4a isolates very close to Egyptian prototype HCV strains, while 1a isolates were homogeneous and clustering to the European and North American genetic lineages. The implications of this study highlight the importance of HCV subtyping as an indispensable tool to monitor the distribution of viral strains, to determine the risk factors of infection prevalence, and to investigate clinical differences of treatment outcomes among intergenotypic and intragenotypic isolates in the treated population.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Almalki

Shahid

Abdalla

et al. 2021

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

show abstract

“…Indeed, Human immunodeficiency virus type 1 (HIV-1) is the first virus shown to be inhibited by siRNA when these molecules target various viral regions [ 54 ]. In addition, numerous regions of HCV’s RNA genome are sensitive to the action of siRNA and PNAs [ 55 , 56 , 57 ].…”

Section: Effect Of These Oligonucleotides On Others Virusesmentioning

confidence: 99%

Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus

et al. 2020

View full text Add to dashboard Cite

Peptide Nucleic Acid (PNAs) and small noncoding RNAs including small interfering RNAs (siRNAs) represent a new class of oligonucleotides considered as an alternative therapeutic strategy in the chronic hepatitis B treatment. Indeed, chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide, despite the availability of an effective prophylactic vaccine. Current therapeutic approaches approved for chronic HBV treatment are pegylated-interferon alpha (IFN)-α and nucleos(t)ide analogues (NAs). Both therapies do not completely eradicate viral infection and promote severe side effects. In this context, the development of new effective treatments is imperative. This review focuses on antiviral activity of both PNAs and siRNAs targeting hepatitis B virus. Thus, we briefly present our results on the ability of PNAs to decrease hepadnaviral replication in duck hepatitis B virus (DHBV) model. Interestingly, other oligonucleotides as siRNAs could significantly inhibit HBV antigen expression in transient replicative cell culture. Because the application of these oligonucleotides as new antiviral drugs has been hampered by their poor intracellular bioavailability, we also discuss the benefits of their coupling to different molecules such as the cell penetrating peptides (CPPs), which were used as vehicles to deliver therapeutic agents into the cells.

show abstract

Immediately early 2 (IE-2) and DNA polymerase SiRNA as virus-specific antiviral against novel transplacental cytomegalovirus strain ALL-03 in vitro

Balakrishnan

Abdullah

Bala

et al. 2021

Infection, Genetics and Evolution

View full text Add to dashboard Cite

Inhibition of hepatitis C virus genotype 4 replication using siRNA targeted to the viral core region and the CD81 cellular receptor

Cited by 7 publications

References 30 publications

Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus

Immediately early 2 (IE-2) and DNA polymerase SiRNA as virus-specific antiviral against novel transplacental cytomegalovirus strain ALL-03 in vitro

Contact Info

Product

Resources

About