Indari Omkar, Jakhmola Shweta, Manivannan Elangovan, Jha Hem Chandra
Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India.
School of Pharmacy, Devi Ahilya Vishwavidyalaya, Indore, India.
Front Pharmacol. 2021 Mar 8;12:632677. doi: 10.3389/fphar.2021.632677. eCollection 2021.
COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.
新冠疫情已呈指数级在全球蔓延，瞬间影响了数百万人。目前，各种药物正在接受研究，以治疗数量急剧增加的新冠患者。这种严峻形势显然需要一种有效的策略，以便快速识别出能成功治疗新冠的药物。因此，药物重新利用是快速发现抗击新冠一线武器的有效方法。该方法的成功应用已使一些临床批准药物被重新用作潜在的抗SARS-CoV-2候选药物。其中几种药物要么是抗疟药、抗病毒药、抗生素，要么是皮质类固醇，它们被重新利用是基于其对抗病毒或减轻肺部炎症的潜力。大量临床试验已登记，以评估这些药物的有效性和临床安全性。到目前为止，一些临床研究已经完成，结果初步得出。世卫组织还开展了一项国际、多国、开放标签的随机试验——四种抗病毒药物的团结试验。然而，团结试验有一些局限性，比如未使用安慰剂，此外，任何药物在某个地区对特定人群可能显示出有效性，但在团结试验分析中可能被忽视。正在进行的随机临床试验可以提供可靠的长期随访结果，这将确定这些药物在不同地区、人群中的临床安全性和临床疗效，并可能有助于全球范围内的新冠治疗研究。本综述全面更新了主要重新利用的药物，即氯喹、羟氯喹、瑞德西韦、洛匹那韦-利托那韦、法匹拉韦、利巴韦林、阿奇霉素、乌米芬诺韦、奥司他韦以及用于对抗SARS-CoV-2的康复期血浆疗法。该综述还总结了这些重新利用药物的抗SARS-CoV-2活性机制的数据，以及临床前和临床研究结果、治疗方案、药代动力学和药物相互作用。
