An Anti-HIV Drug Is Highly Effective Against SARS-CoV-2 In Vitro and Has Potential Benefit for Long COVID Treatment
Khaidarov S. Hejran A.B. Moldakaryzova A. Izmailova S. Nurgaliyeva B. Beisenova A. Mustafaeva A. Nurzhanova K. Belova Y. Satbayeva E. Aidarov A. Ossikbayeva S. Kukubassov Y. Amankulov J. Goncharova T. Yeszhan B. Tulman E. Tazhibayeva K.N. Sadykova A. Kozhabergenov N. Burashev Y.
September 2025Multidisciplinary Digital Publishing Institute (MDPI)
Viruses
2025#17Issue 9
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 (CC50, EC50, 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 log10 (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.
antiviral therapeutics , combination index (CI) , cytostatic effect (CE) , cytotoxic concentration (CC) , drug repurposing , in vitro screening , pharmacological indices , SARS-CoV-2 , synergistic drug combinations , therapeutic window
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Biology Faculty Building, Department of Biology and Biotechnology, Al-Farabi Kazakh National University, Al-Farabi Street 71, Almaty, 050040, Kazakhstan
Department of Molecular Biology and Medical Genetics, Kazakh National Medical University Named After S.D. Asfendiyarov, Zheltoksan 37A Street, Almaty, 050012, Kazakhstan
Department of Biology, Faculty of Education, Helmand University, Lashkar Gah, 3901, Afghanistan
School of General Medicine 1, Kazakh National Medical University Named After S.D. Asfendiyarov, Tole-bi Street 94, No. 4 Academic Building, Room 206, Almaty, 050012, Kazakhstan
Department of Propaedeutics of Internal Medicine, Kazakh National Medical University Named After S.D. Asfendiyarov, Tole-bi Street 94, Almaty, 050012, Kazakhstan
Department of Pharmacology, Kazakh National Medical University Named After S.D. Asfendiyarov, Tole-bi Street 94, Almaty, 050012, Kazakhstan
Department of Oncology, Kazakh-Russian Medical University, Almaty, 050012, Kazakhstan
Kazakh Institute of Oncology and Radiology (KazIOR), Almaty, 050022, Kazakhstan
Department of Anatomy, Physiology, and Sports Medicine, Kazakh Academy of Sports and Tourism (KazAST), Abay Street 83/85, Almaty, 050022, Kazakhstan
Department of Pathobiology and Veterinary Science, Atwater Laboratory, University of Connecticut, Room A110, Storrs, 06269, CT, United States
Almaty Regional Multidisciplinary Clinic, Department of Surgery, Faculty of Medicine and Health, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Department of General Medical Practice, School of Medicine and Healthcare, Al-Farabi University, Almaty, 050040, Kazakhstan
Republican Blood Center, Utepova Street 1, Almaty, 050060, Kazakhstan
Research Institute for Biological Safety Problems, Gvardeyskyi, Kordai, 080409, Kazakhstan
Biology Faculty Building
Department of Molecular Biology and Medical Genetics
Department of Biology
School of General Medicine 1
Department of Propaedeutics of Internal Medicine
Department of Pharmacology
Department of Oncology
Kazakh Institute of Oncology and Radiology (KazIOR)
Department of Anatomy
Department of Pathobiology and Veterinary Science
Almaty Regional Multidisciplinary Clinic
Department of General Medical Practice
Republican Blood Center
Research Institute for Biological Safety Problems
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