{"doi":"10.3389/fmicb.2020.617375","title":"Prevalence of Naturally-Occurring NS5A and NS5B Resistance-Associated Substitutions in Iranian Patients With Chronic Hepatitis C Infection","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>Hepatitis C virus (HCV), non-structural 5A (NS5A), and non-structural 5B (NS5B) resistance-associated substitutions (RASs) are the main causes of failure to direct-acting antiviral agents (DAAs). NS5A and NS5B RASs can occur in patients with HCV infection naturally and before exposure to DAAs.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>This study aimed to evaluate naturally-occurring NS5A and NS5B RASs in Iranian patients with HCV genotype 1a (HCV-1a) and -3a infections.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this cross-sectional study, viral RNA was extracted from serum specimens. NS5A and NS5B regions were amplified using RT-PCR followed by DNA sequencing. The results of nucleotide sequences were aligned against reference sequences of HCV-1a and -3a and the amino acid substitutions were analyzed using geno2pheno [hcv] web application.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 135 patients with hepatitis C, NS5A amino acid substitutions/RASs were identified in 26.4% and 15.9% of patients with HCV-1a and -3a infections, respectively. The identified amino acid substitutions/RASs in the NS5A region of patients with HCV-1a infection were M28T/V/I 11.1%, Q30R/H 4.2%, L31M 1.4%, and H58Y/P/C/D/Q/S/T 16.7%. Y93H substitution was not found in HCV-1a sequences. In patients with HCV-3a infection, NS5A amino acid substitutions/RASs were A30T/K 9.5%, L31F 1.6%, P58S/T/C 3.2%, Y93H 3.2%, and Y93N 3.2%. No resistance substitutions were identified in NS5B sequences from patients with HCV-1a and -3a infections.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In this study, baseline amino acid substitutions/RASs were only identified in the NS5A region in Iranian patients with HCV-1a and -3a infections, and the prevalence of these amino acid substitutions/RASs were in accordance with similar studies. There were no RASs in the HCV-1a and -3a NS5B region.</jats:p></jats:sec>","journal":"Frontiers in Microbiology","year":2021,"id":19547,"datarank":0.3470101876693364,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.07824626728512812,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.07824626728512812,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":73226,"name":"Heidar Sharafi","orcid":"0000-0001-9177-9117","position":1,"is_corresponding":false},{"id":132062,"name":"Golnaz Bahramali","orcid":null,"position":2,"is_corresponding":false},{"id":132063,"name":"FaridehSadat SajadianFard","orcid":null,"position":3,"is_corresponding":false},{"id":132064,"name":"Nafiseh Sadat Asadi","orcid":null,"position":4,"is_corresponding":false},{"id":73136,"name":"Seyed Moayed Alavian","orcid":"0000-0002-4443-6602","position":5,"is_corresponding":false},{"id":132065,"name":"Vahid Iranpur Mobarakeh","orcid":null,"position":6,"is_corresponding":false},{"id":132066,"name":"Seyedeh Zahra Moravej","orcid":null,"position":7,"is_corresponding":false},{"id":132061,"name":"Pooneh Rahimi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33584581","pmcid":"PMC7876467","openalex_id":"https://openalex.org/W3129017820","authors":[],"funders":[],"total_grants":0,"fwci":0.5823,"citation_percentile":0.64302661,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.3389/fmicb.2020.617375","host_type":"journal"},{"url":"https://doi.org/10.3389/fmicb.2020.617375","host_type":"GOLD"},{"url":"https://doi.org/10.3389/fmicb.2020.617375","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fmicb.2020.617375/full","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33584581","host_type":"repository"},{"url":"https://doaj.org/article/7c9d900ff2894eeab1e7ede7e0e3cf35","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7876467","host_type":"repository"},{"url":"https://www.frontiersin.org/articles/10.3389/fmicb.2020.617375/pdf","host_type":"Unpaywall"},{"url":"https://europepmc.org/articles/PMC7876467","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7876467?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Hepatitis C virus research","HIV/AIDS drug development and treatment","Influenza Virus Research Studies","Medicine"],"mesh_terms":[],"keywords":["NS5A","NS5B","Hepatitis C virus","Virology","Amino acid","Biology","Hepacivirus","Amino acid substitution","Drug resistance","Hepatitis C","Virus","Medicine","Genetics","Mutation","Gene","HCV","Direct-acting Antiviral Agents","Resistance-associated Substitution"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-04T04:43:41.053311Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}