一种抗HIV药物在体外对SARS-CoV-2具有高度有效性，对长期新冠治疗可能有益。

An Anti-HIV Drug Is Highly Effective Against SARS-CoV-2 In Vitro and Has Potential Benefit for Long COVID Treatment.

作者信息

Khaidarov Saken, Hejran Abdul Bari, Moldakaryzova Aizhan, Izmailova Slu, Nurgaliyeva Bayan, Beisenova Aizhan, Mustafaeva Aigul, Nurzhanova Kuanysh, Belova Yelena, Satbayeva Elmira, Aidarov Askar, Ossikbayeva Saniya, Kukubassov Yerlan, Amankulov Jandos, Goncharova Tatyana, Yeszhan Banu, Tulman Edan, Tazhibayeva Karlygash N, Sadykova Assel, Kozhabergenov Nurlan, Burashev Yerbol

机构信息

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.

出版信息

Viruses. 2025 Aug 27;17(9):1170. doi: 10.3390/v17091170.

DOI:10.3390/v17091170

PMID:41012598

Abstract

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, EC, 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 (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.

摘要

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的持续进化需要新的抗病毒策略。本研究评估了抗HIV前体药物替诺福韦酯（TDF）和替诺福韦艾拉酚胺（TAF）对SARS-CoV-2的重新利用，评估了关键药理学指标（CC、EC、细胞抑制作用和治疗窗口）。在Vero E6细胞中进行的体外筛选测量了细胞毒性（通过CCK-8/MTT试验）以及对哈萨克斯坦B.1和武汉毒株的抗病毒活性。TDF（50μg/mL）可使高病毒载量（感染复数为2）降低约2个对数（100%抑制），细胞毒性最小（存活率≥75%）。TAF在50μg/mL时实现了近乎完全的抑制（100%抑制），在较低病毒载量（感染复数为0.01）时表现出剂量依赖性抑制（68-100%）。两种前体药物在延长暴露时间（96小时）后均表现出增强的抗病毒活性。协同评估显示出良好的联合指数（CI<1）。电子显微镜证实治疗后病毒粒子的完整性。这些发现突出了TDF和TAF作为抗SARS-CoV-2的有前景的候选药物，尤其在靶向淋巴样储存库方面具有潜力，这些部位与可能导致长期新冠发病机制的持续性病毒储存库有关。需要进一步的临床验证。