ArticleMolecules (Basel, Switzerland)2022
The Nucleoside/Nucleotide Analogs Tenofovir and Emtricitabine Are Inactive against SARS-CoV-2.
Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Mechanism of Inhibition of the Active Triphosphate Form of 2'-α-Fluoro,2'-β-bromouridine against Yellow Fever Virus RNA-Dependent RNA Polymerase.ACS infectious diseases · 2025Article
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- Association between Hepatitis B virus infection and COVID-19: outcomes from clinical analysis and online survey from Beijing, China.BMC infectious diseases · 2024Article
- Effects of entecavir and tenofovir disoproxil fumarate on the incidence and severity of COVID-19 in patients with chronic hepatitis B.BMC infectious diseases · 2023Article
- Potential RNA-dependent RNA polymerase (RdRp) inhibitors as prospective drug candidates for SARS-CoV-2.European journal of medicinal chemistry · 2023Review
- Drug Repurposing and Observational Studies: The Case of Antivirals for the Treatment of COVID-19.Annals of internal medicine · 2023Review
- Effects of natural polymorphisms in SARS-CoV-2 RNA-dependent RNA polymerase on its activity and sensitivity to inhibitors in vitro.Biochimie · 2023Article
- Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase.Computational and structural biotechnology journal · 2023Review
- Inspection on the Mechanism of SARS-CoV-2 Inhibition by Penciclovir: A Molecular Dynamic Study.Molecules (Basel, Switzerland) · 2022Article
- An update on inhibitors targeting RNA-dependent RNA polymerase for COVID-19 treatment: Promises and challenges.Biochemical pharmacology · 2022Review
- Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
The urgent response to the COVID-19 pandemic required accelerated evaluation of many approved drugs as potential antiviral agents against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using cell-based, biochemical, and modeling approaches, we studied the approved HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTIs) tenofovir (TFV) and emtricitabine (FTC), as well as prodrugs tenofovir alafenamide (TAF) and tenofovir disoproxilfumarate (TDF) for their antiviral effect against SARS-CoV-2. A comprehensive set of in vitro data indicates that TFV, TAF, TDF, and FTC are inactive against SARS-CoV-2. None of the NRTIs showed antiviral activity in SARS-CoV-2 infected A549-hACE2 cells or in primary normal human lung bronchial epithelial (NHBE) cells at concentrations up to 50 µM TAF, TDF, FTC, or 500 µM TFV. These results are corroborated by the low incorporation efficiency of respective NTP analogs by the SARS-CoV-2 RNA-dependent-RNA polymerase (RdRp), and lack of the RdRp inhibition. Structural modeling further demonstrated poor fitting of these NRTI active metabolites at the SARS-CoV-2 RdRp active site. Our data indicate that the HIV-1 NRTIs are unlikely direct-antivirals against SARS-CoV-2, and clinicians and researchers should exercise caution when exploring ideas of using these and other NRTIs to treat or prevent COVID-19.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.