Hala Rady Ahmed1, Nancy G F M Waly1, Rehab Mahmoud Abd El-Baky1,2, Ramadan Yahia2, Helal F Hetta3,4, Amr M Elsayed5, Reham Ali Ibrahem1. 1. Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt. 2. Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia, Egypt. 3. Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt. 4. Department of Medical Microbiology and Immunology, Faculty of Medicine, Merit University, Sohag, Egypt. 5. Tropical Medicine and Gastroenterology, Faculty of Medicine, Minia University, Minia, Egypt.
Abstract
BACKGROUND: NS5B polymerase inhibitors represent the cornerstone of the present treatment of Hepatitis C virus infection (HCV). Naturally occurring substitution mutations to NS5B inhibitors have been recorded. The current study intended to demonstrate possible natural direct acting antiviral (DAA)-mutations of the HCV NS5B region in HCV patients in Minia governorate, Egypt. METHODS: Samples were collected from 27 treatment-naïve HCV patients and 8 non-responders. Out of 27 treatment-naïve patients, 17 NS5B sequences (amino acids 221-345) from treatment-naïve patients and one sample of non-responders were successfully amplified. Nucleotide sequences have been aligned, translated into amino acids, and compared to drug resistance mutations reported in the literature. RESULTS: NS5B amino acid sequence analysis ensures several novel NS5B mutations existence (more than 40 substitution mutations) that have not been previously documented to be correlated with a resistant phenotype. It was found that K304R (82.4%), E327D and P300T (76.5% each) substitutions were the most distributed in the tested samples, respectively. S282T, the major resistance mutation that induces high sofosbuvir-resistance level in addition to other reported mutations (L320F/C) and (C316Y/N) were not recognized. Q309R mutation is a ribavirin-associated resistance, which was recognized in one strain (5.9%) of genotype 1g sequences. Besides, one substitution mutation (E237G) was identified in the successfully amplified non-responder sample. CONCLUSION: Our study showed various combinations of mutations in the analyzed NS5B genes which could enhance the possibility of therapy failure in patients administered regimens including multiple DAA.
BACKGROUND: NS5B polymerase inhibitors represent the cornerstone of the present treatment of Hepatitis C virus infection (HCV). Naturally occurring substitution mutations to NS5B inhibitors have been recorded. The current study intended to demonstrate possible natural direct acting antiviral (DAA)-mutations of the HCV NS5B region in HCV patients in Minia governorate, Egypt. METHODS: Samples were collected from 27 treatment-naïve HCV patients and 8 non-responders. Out of 27 treatment-naïve patients, 17 NS5B sequences (amino acids 221-345) from treatment-naïve patients and one sample of non-responders were successfully amplified. Nucleotide sequences have been aligned, translated into amino acids, and compared to drug resistance mutations reported in the literature. RESULTS: NS5B amino acid sequence analysis ensures several novel NS5B mutations existence (more than 40 substitution mutations) that have not been previously documented to be correlated with a resistant phenotype. It was found that K304R (82.4%), E327D and P300T (76.5% each) substitutions were the most distributed in the tested samples, respectively. S282T, the major resistance mutation that induces high sofosbuvir-resistance level in addition to other reported mutations (L320F/C) and (C316Y/N) were not recognized. Q309R mutation is a ribavirin-associated resistance, which was recognized in one strain (5.9%) of genotype 1g sequences. Besides, one substitution mutation (E237G) was identified in the successfully amplified non-responder sample. CONCLUSION: Our study showed various combinations of mutations in the analyzed NS5B genes which could enhance the possibility of therapy failure in patients administered regimens including multiple DAA.
Authors: Helal F Hetta; Mohamed A Mekky; Nasr K Khalil; Wegdan A Mohamed; Mohamed A El-Feky; Shabaan H Ahmed; Enas A Daef; Ahmed Medhat; Mahmoud I Nassar; Kenneth E Sherman; Mohamed Tarek M Shata Journal: J Med Microbiol Date: 2016-05-10 Impact factor: 2.472
Authors: Michael Manns; Didier Samuel; Edward J Gane; David Mutimer; Geoff McCaughan; Maria Buti; Martín Prieto; José Luis Calleja; Markus Peck-Radosavljevic; Beat Müllhaupt; Kosh Agarwal; Peter Angus; Eric M Yoshida; Massimo Colombo; Mario Rizzetto; Hadas Dvory-Sobol; Jill Denning; Sarah Arterburn; Phillip S Pang; Diana Brainard; John G McHutchison; Jean-François Dufour; Hans Van Vlierberghe; Bart van Hoek; Xavier Forns Journal: Lancet Infect Dis Date: 2016-02-18 Impact factor: 25.071
Authors: Minesh Mehta; Helal F Hetta; Enass A Abdel-Hameed; Susan D Rouster; MdMonir Hossain; Mohamed A Mekky; Nasr K Khalil; Wegdan A Mohamed; Mohamed A El-Feky; Shabaan H Ahmed; Enas A Daef; Mohamed A El-Mokhtar; Sayed F Abdelwahab; Ahmed Medhat; Kenneth E Sherman; Mohamed Tarek M Shata Journal: Arch Virol Date: 2016-08-20 Impact factor: 2.574