An Anti-HIV Drug Is Highly Effective Against SARS-CoV-2 In Vitro and Has Potential Benefit for Long COVID Treatment
The persistent evolution of SARS-CoV-2 necessitates novel antiviral strategies. This study evaluated the anti-HIV prodrugs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) for repurposing against SARS-CoV-2, assessing key pharmacological indices (CC<sub>50</sub>, EC<sub>50</sub>, cytostatic effect, and therapeutic window). In vitro screening in Vero E6 cells measured cytotoxicity (via CCK-8/MTT assays) and antiviral activity against Kazakh B.1 and Wuhan strains. TDF (50 µg/mL) reduced high viral loads (MOI 2) by ~2 log<sub>10</sub> (100% inhibition), with minimal cytotoxicity (≥75% viability). TAF achieved near-complete suppression (100% inhibition) at 50 µg/mL, exhibiting dose-dependent inhibition (68-100%) at lower viral loads (MOI 0.01). Both prodrugs showed enhanced antiviral activity with prolonged exposure (96 h). Synergy assessments demonstrated favourable combination indices (CI < 1). Electron microscopy confirmed virion integrity post-treatment. These findings highlight TDF and TAF as promising candidates against SARS-CoV-2, with particular potential for targeting lymphoid reservoirs-sites implicated in persistent viral reservoirs that may contribute to long COVID pathogenesis. Further clinical validation is warranted.
Authors
- Karlygash Tazhibayeva (ORCID: https://orcid.org/0000-0003-4947-3717)
- A. Aidarov (ORCID: https://orcid.org/0000-0001-5081-1264)
- S. Khaidarov (ORCID: https://orcid.org/0000-0001-7770-8427)
- Aigul Mustafaeva (ORCID: https://orcid.org/0000-0002-1663-920X)
- Assel Sadykova (ORCID: https://orcid.org/0000-0002-4662-0817)
- E. R. Tulman (ORCID: https://orcid.org/0000-0002-2682-5145)
- Yerlan Kukubassov
- Jandos Amankulov (ORCID: https://orcid.org/0000-0001-7389-3119)
- Nurlan Kozhabergenov (ORCID: https://orcid.org/0000-0001-6299-9399)
- S. Ossikbayeva (ORCID: https://orcid.org/0000-0003-1420-7486)
- Aizhan Beisenova (ORCID: https://orcid.org/0000-0002-8128-154X)
- T. Goncharova (ORCID: https://orcid.org/0000-0003-2524-8750)
- Aizhan Moldakaryzova (ORCID: https://orcid.org/0000-0003-0186-978X)
- B. G. Yeszhan (ORCID: https://orcid.org/0000-0001-8769-5551)
- Yerbol Burashev (ORCID: https://orcid.org/0000-0002-4701-1992)
- E.M. Satbayeva (ORCID: https://orcid.org/0000-0002-5521-5776)
- Abdul-Bari Hejran (ORCID: https://orcid.org/0009-0000-0443-0305)
- Slu Izmailova
- Bayan Nurgaliyeva (ORCID: https://orcid.org/0000-0003-2555-8644)
- Kuanysh Nurzhanova
- Yelena Belova
Institutions
- University of Connecticut (US)
- Al-Farabi Kazakh National University (KZ)
- Kazakh National Medical University (KZ)
- Turan University (KZ)
- Bost University (AF)
- Kazakh Academy of Sport and Tourism (KZ)
- Kazakh Institute of Oncology and Radiology (KZ)
- Kazakhstan Medical University (KZ)
- Semey Medical University (KZ)
Publication Details
- Journal
- Viruses
- Published
- 2025-08-27
- DOI
- https://doi.org/10.3390/v17091170
- Citations
- 1
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 1.88