Acharya Arpan, Kutateladze Tatiana G, Byrareddy Siddappa N
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center; Omaha, NE 68131, USA.
Department of Pharmacology, University of Colorado School of Medicine; Aurora, CO 80045, USA.
Clin Transl Discov. 2022 Jun;2(2). doi: 10.1002/ctd2.66. Epub 2022 May 6.
The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has resulted in more than 500 million cases and 6 million deaths. Several antiviral therapies and vaccines have been developed to mitigate the spread of this infection. However, new approaches are required to battle emerging SARS-CoV-2 variants containing mutations that can reduce the vaccines' efficacy. The use of a combination of viral drugs with inhibitors of the mTOR signaling pathways has emerged as one of the promising novel approaches. We recently showed that SF2523, a dual activity small molecule that inhibits PI3K and BRD4, acts synergistically with the antiviral drugs remdesivir and MU-UNMC-2. Our findings suggest that the mTOR pathways are necessary for SARS-CoV-2 pathogenesis in human cells and targeting PI3K/BET (bromodomain and extra-terminal domain proteins) alone or combined with antiviral therapies is beneficial in mitigating SARS-CoV-2 and its variants of concern (VOCs).
由新型冠状病毒SARS-CoV-2引起的COVID-19大流行已导致超过5亿例感染和600万人死亡。已经开发了几种抗病毒疗法和疫苗来减轻这种感染的传播。然而，需要新的方法来对抗出现的含有可降低疫苗效力的突变的SARS-CoV-2变体。将病毒药物与mTOR信号通路抑制剂联合使用已成为一种有前景的新方法。我们最近发现，SF2523是一种抑制PI3K和BRD4的双活性小分子，它与抗病毒药物瑞德西韦和MU-UNMC-2协同作用。我们的研究结果表明，mTOR通路对于SARS-CoV-2在人类细胞中的发病机制是必要的，单独靶向PI3K/BET（溴结构域和额外末端结构域蛋白）或与抗病毒疗法联合使用，有利于减轻SARS-CoV-2及其关注变体（VOCs）。
