Wehbe Zena, Wehbe Maya, Iratni Rabah, Pintus Gianfranco, Zaraket Hassan, Yassine Hadi M, Eid Ali H
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
Department of Internal Medicine, Basingstoke & North Hampshire Hospital, Basingstoke, United Kingdom.
Front Immunol. 2021 Mar 30;12:663586. doi: 10.3389/fimmu.2021.663586. eCollection 2021.
As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, have been approved for emergency use in various countries. However, the slow roll-out of vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. Moreover, vaccines are important tools for preventing the disease but therapeutic tools to treat patients are also needed. As such, since the beginning of the pandemic, repurposed FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to their known safety profiles and potential anti-viral effects. One of these drugs is ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral activity against various viruses including SARS-CoV-2. In this review, we delineate the story of how this antiparasitic drug was eventually identified as a potential treatment option for COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning points in past research that provided initial 'hints' for IVM's antiviral activity and its molecular mechanism of action- and finally, we culminate with the current clinical findings.
截至2021年1月,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)已在全球造成超过200万人死亡。因此,迫切需要疫苗和治疗方法来减轻新冠病毒病(COVID-19)的负担。包括信使核糖核酸(mRNA)疫苗、载体疫苗和灭活疫苗在内的几种疫苗已在各国获批紧急使用。然而,疫苗推出速度缓慢和全球供应不足仍然是扭转疫情局势的一项挑战。此外,疫苗是预防该疾病的重要工具,但也需要治疗患者的治疗手段。因此,自疫情开始以来,由于已获美国食品药品监督管理局(FDA)批准的药物具有已知的安全性和潜在的抗病毒作用,人们一直在寻找将其重新用于治疗COVID-19的潜在治疗方案。其中一种药物是伊维菌素(IVM),一种20世纪70年代研制的抗寄生虫药物。IVM后来对包括SARS-CoV-2在内的多种病毒发挥了抗病毒活性。在这篇综述中,我们阐述了这种抗寄生虫药物最终如何被确定为COVID-19潜在治疗方案的过程。我们回顾了SARS-CoV-2的生命周期、核衣壳蛋白的作用、过去研究中的转折点,这些转折点为IVM的抗病毒活性及其分子作用机制提供了最初的“线索”,最后,我们总结了当前的临床研究结果。