Dissection of two drug-targeted regions of Hepatitis C virus subtype 4a infecting Egyptian patients
- PDF / 1,552,488 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 55 Downloads / 111 Views
ORIGINAL PAPER
Dissection of two drug‑targeted regions of Hepatitis C virus subtype 4a infecting Egyptian patients Radwa R. El‑Tahan1 · Ahmed M. Ghoneim1 · Hosam Zaghloul2 Received: 21 December 2019 / Accepted: 16 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Recently, treatment of HCV infection has been improved after the development of direct acting antivirals (DAAs) which target different viral proteins (NS3-4A, NS5A and NS5B). The activity and effectiveness of these DAAs are affected by the presence of resistance associated substitutions (RASs). This study aimed to characterize HCV genotypes circulating among Egyptian HCV patients, to dissect the full sequences of HCV NS3-4A and NS5B regions, and to characterize RASs associated with NS3-4A and NS5B inhibitors in HCV treatment-naïve patients. Genotyping of 80 HCV samples from treatmentnaïve patients was done using restriction fragment length polymorphism and phylogenetic analysis based on some full NS5B sequences. Results showed the prevalence of HCV subtype 4a. Twenty four new full sequences of NS3-4A and NS5B regions of subtype 4a were deposited in the GenBank database. In general, the substitutions associated with NS3-4A-targeting drugs were absent predicting possible responsiveness of Egyptian HCV patients to these drugs. In addition, the absence of amino acid substitutions associated with resistance to Sofosbuvir may predict good response to treatment with Sofosbuvir. Some amino acid substitutions associated with resistance to different classes of non-nucleoside inhibitors were detected. Further investigations on treated Egyptian HCV patients may evaluate the effectiveness of the massively used drugs. Many predicted T-cell-binding epitopes in NS3-4A and NS5B regions were found to be highly conserved in the currently studied isolates; a finding that might be important for HCV vaccine development. We demonstrated potential NS3 epitopes that could be used in engineering T cells against HCV epitopes. Keywords HCV · Genotypes · NS3-4A · NS5B · Antiviral drugs
Introduction
Edited by Wolfram H. Gerlich. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11262-020-01776-y) contains supplementary material, which is available to authorized users. * Ahmed M. Ghoneim [email protected] Radwa R. El‑Tahan [email protected] Hosam Zaghloul [email protected] 1
Zoology Department, Faculty of Science, Damietta University, New Damietta, P.O. 34517, Damietta, Egypt
Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2
Hepatitis C virus (HCV) is a global health burden and around 71 million people suffer from chronic hepatitis C infection [1]. HCV is a significant causative agent for liver cirrhosis, hepatocellular carcinoma, and finally mortality and approximately 400 thousand people die from HCV each year [1]. HCV belongs to Flaviviridae family and forms its own genus hepacivirus. HCV is a 9.6 kb single positive stranded RNA v
Data Loading...
