Antiretroviral drug activity and potential for pre-exposure prophylaxis against COVID-19 and HIV infection.
Antiretroviral drug activity and potential for pre-exposure prophylaxis against COVID-19 and HIV infection.
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DOI：
10.1080/07391102.2021.1901144
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发表时间：
2022-10
影响因子：
4.4
通讯作者：
Nixon DF
中科院分区：
文献类型：
--
作者：
Copertino DC Jr;Casado Lima BC;Duarte RRR;Powell TR;Ormsby CE;Wilkin T;Gulick RM;de Mulder Rougvie M;Nixon DF
COVID-19 是由 SARS-CoV-2 引起的疾病，已导致全球 2,477,000 人死亡，而且这一数字还在迅速增加。目前正在进行紧急研究，以确定新的抗病毒药物、重新利用现有药物或确定可以针对过度活跃的免疫反应的药物。抗逆转录病毒药物 (ARV) 已在过去的人类冠状病毒感染中进行了测试，也针对 SARS-CoV-2 进行了测试，但洛匹那韦和利托那韦的试验未能显示出对 COVID-19 的任何临床益处。然而，关于 HIV 感染者的 COVID-19 病程的数据有限，一些研究显示，服用某些抗逆转录病毒疗法的患者的死亡率有所下降。我们假设洛匹那韦和利托那韦以外的抗逆转录病毒药物可能对防止 COVID-19 的进展有一定的保护作用。在这里，我们使用化学信息学分析来预测哪些抗逆转录病毒药物会结合并可能抑制 SARS-CoV-2 主要蛋白酶 (Mpro) 或 RNA 依赖性 RNA 聚合酶 (RdRp)。预计能结合 SARS-CoV-2 Mpro 的药物包括蛋白酶抑制剂阿扎那韦和茚地那韦。预测结合 RdRp 催化位点的抗逆转录病毒药物包括核苷逆转录酶抑制剂、阿巴卡韦、恩曲他滨、齐多夫定和替诺福韦。如果在体外和临床试验中证明现有或新的抗逆转录病毒药物组合可以抑制 SARS-CoV-2，则有可能预防或改善 COVID-19 的病程。需要进一步研究来确定抗逆转录病毒药物治疗或预防 SARS-CoV-2 感染的活性。
COVID-19 is the disease caused by SARS-CoV-2 which has led to 2,477,000 deaths worldwide, a number which is rapidly increasing. Urgent studies to identify new antiviral drugs, repurpose existing drugs, or identify drugs that can target the overactive immune response are ongoing. Antiretroviral drugs (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but a trial of lopinavir and ritonavir failed to show any clinical benefit in COVID-19. However, there is limited data as to the course of COVID-19 in people living with HIV, with some studies showing a decreased mortality for those taking certain ARV regimens. We hypothesized that ARVs other than lopinavir and ritonavir might be responsible for some protection against the progression of COVID-19. Here, we used chemoinformatic analyses to predict which ARVs would bind and potentially inhibit the SARS-CoV-2 main protease (Mpro) or RNA-dependent-RNA-polymerase (RdRp) enzymes in silico. The drugs predicted to bind the SARS-CoV-2 Mpro included the protease inhibitors atazanavir and indinavir. The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir. Existing or new combinations of antiretroviral drugs could potentially prevent or ameliorate the course of COVID-19 if shown to inhibit SARS-CoV-2 in vitro and in clinical trials. Further studies are needed to establish the activity of ARVs for treatment or prevention of SARS-CoV-2 infection.
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影响因子：
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