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Basic Characteristics of Mutations
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Mutation Site
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L199V |
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Mutation Site Sentence
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Moreover, there are other mutations in the RT domains of these clones that include rtH55R, rtD131N, rtL164M, rtI169T, rtT184L, rtL199V and rtL269I for 69-2 and rtH55R, rtM129L, rtT184L, rtQ267L, rtL269I and rtK333Q for 71-3 (Figure 3a). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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P
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Hepatitis B Virus Infection
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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Entecavir(ETV) |
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Location
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- |
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Literature Information
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PMID
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35884942
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Title
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Susceptibility of Drug Resistant Hepatitis B Virus Mutants to Besifovir
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Author
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Won J,Lee AR,Dezhbord M,Lee DR,Kim SH,Kim JC,Park S,Kim N,Jae B,Kim KH
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Journal
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Biomedicines
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Journal Info
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2022 Jul 7;10(7):1637
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Abstract
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Currently, interferon alpha and nucleos(t)ide analogues (NAs) are clinically available to treat hepatitis B virus (HBV) infection. Several NAs, including lamivudine (LMV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF or TAF) have been approved and administered to chronic hepatitis B (CHB) patients. NAs inhibit HBV DNA synthesis by targeting the reverse transcriptase (RT) domain of HBV polymerase. Several mutations in the RT domain which lead to drug resistance against NAs have been reported, even for TDF and TAF which are highly potent with very low resistance rate. Besifovir (BFV) is a new antiviral dGMP analogue able to be used as a new NA drug for the control of CHB infection. Drug resistance to BFV is not well known due to its shorter duration of clinical use. Recently, we reported that rtL180M (M) and rtM204V (V) mutations, already resistant to LMV, are associated with BFV resistance. However, the susceptibility to BFV of previously known HBV mutants resistant to various drugs has not been studied. To investigate this, we performed in vitro drug susceptibility assays using natural and artificial mutants that are associated with resistance to LMV, ADV, ETV or TDF. As a result, LMV-resistant mutants were not susceptible to BFV and ETV-resistant clones showed partial resistance against BFV as well. However, ADV-resistant mutants were highly sensitive to BFV. In case of tenofovir-resistant mutations, the HBV mutants harboring primary mutations to tenofovir resistance were susceptible to BFV. Therefore, our study revealed that BSV may serve as an alternative drug for patients with ADV-, ETV-, TDF- or TAF-resistance.
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Sequence Data
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-
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