Bernstein Lawrence R, Zhang Leike
Gallixa LLC, Menlo Park, CA, USA.
CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
Antivir Chem Chemother. 2020 Jan-Dec;28:2040206620983780. doi: 10.1177/2040206620983780.
Gallium has demonstrated strong anti-inflammatory activity in numerous animal studies, and has also demonstrated direct antiviral activity against the influenza A H1N1 virus and the human immunodeficiency virus (HIV). Gallium maltolate (GaM), a small metal-organic coordination complex, has been tested in several Phase 1 clinical trials, in which no dose-limiting or other serious toxicity was reported, even at high daily oral doses for several months at a time. For these reasons, GaM may be considered a potential candidate to treat coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus and can result in severe, sometimes lethal, inflammatory reactions. In this study, we assessed the ability of GaM to inhibit the replication of SARS-CoV-2 in a culture of Vero E6 cells.
The efficacy of GaM in inhibiting the replication of SARS-CoV-2 was determined in a screening assay using cultured Vero E6 cells. The cytotoxicity of GaM in uninfected cells was determined using the Cell Counting Kit-8 (CCK-8) colorimetric assay.
The results showed that GaM inhibits viral replication in a dose-dependent manner, with the concentration that inhibits replication by 50% (EC) being about 14 µM. No cytotoxicity was observed at concentrations up to at least 200 µM.
The activity of GaM against SARS-CoV-2, together with GaM's known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.
镓在众多动物研究中已显示出强大的抗炎活性，并且还对甲型H1N1流感病毒和人类免疫缺陷病毒（HIV）表现出直接抗病毒活性。苹果酸镓（GaM）是一种小型金属有机配位化合物，已在多项1期临床试验中进行了测试，在这些试验中，即使一次连续数月每日口服高剂量，也未报告剂量限制或其他严重毒性。基于这些原因，GaM可能被视为治疗2019冠状病毒病（COVID-19）的潜在候选药物，该疾病由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起，可导致严重的、有时甚至致命的炎症反应。在本研究中，我们评估了GaM在Vero E6细胞培养物中抑制SARS-CoV-2复制的能力。
在使用培养的Vero E6细胞的筛选试验中确定GaM抑制SARS-CoV-2复制的效力。使用细胞计数试剂盒8（CCK-8）比色法测定GaM在未感染细胞中的细胞毒性。
结果表明，GaM以剂量依赖的方式抑制病毒复制，抑制复制50%的浓度（EC）约为14µM。在高达至少200µM的浓度下未观察到细胞毒性。
GaM对SARS-CoV-2的活性以及GaM已知的抗炎活性，为在COVID-19患者中测试GaM提供了依据。
