Hurst Brett L, Dickinson Douglas, Hsu Stephen
Institute of Antiviral Research, Utah State University. Logan, UT. USA.
Camellix Research Laboratory, Augusta, GA. USA.
Microbiol Infect Dis. 2021;5(2). doi: 10.33425/2639-9458.1116.
SARS-CoV-2, the novel coronavirus responsible for the COVID-19 pandemic, caused >26 million cases in the United States and >437,000 deaths as of Jan 30, 2020. Worldwide by that date, there had been 102 million cases of infections, and deaths had climbed to 2.21 million. Mutated variants of SARS-CoV-2 that have emerged from the United Kingdom, Brazil, and South Africa are associated with higher transmission rates and associated deaths. Therefore, novel therapeutic and prophylactic methods against SARS-CoV-2 are in urgent need. While some antiviral drugs, such as Remdesivir, provide relief to certain patient populations, other existing antiviral drugs or combinations of FDA approved pharmaceuticals have yet to show clinical efficacy against COVID-19. Compounds that possess strong and broad antiviral properties with different mechanisms of action against respiratory viruses may provide novel approaches to combat SARS-CoV-2 and its variants, especially if the compounds are classified as generally recognized as safe (GRAS). A large body of evidence indicates a promising potential for the use of epigallocatechin-3-gallate (EGCG) and its derivatives as effective agents against infections from a wide range of pathogenic viruses. However, EGCG or its derivatives have not been tested directly against SARS-CoV-2. The current study was designed to evaluate the potential antiviral activity of EGCG against SARS-CoV-2 infection in primate epithelial cells. Methods applied in the study include cytopathic effect (CPE) assay and virus yield reduction (VYR) assays using Vero 76 (green monkey epithelial cells) and Caco-2 (human epithelial cells) cell lines, respectively. The results demonstrated that EGCG at 0.27 μg/ml (0.59 μM) inhibited SARS-CoV-2 infection in Vero 76 cells by 50% (i.e., EC50=0.27 μg/ml). EGCG also inhibited SARS-CoV-2 infection in Caco-2 cells with EC90=28 μg/ml (61 μM). These results, to the best of our knowledge, are the first observations on the antiviral activities of EGCG against SARS-CoV-2, and suggest that EGCG and its derivatives could be used to combat COVID-19 and other respiratory viral infection-induced illness, pending and clinical studies.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是引发新冠疫情的新型冠状病毒,截至2020年1月30日,在美国已导致超过2600万例感染和超过43.7万例死亡。截至该日,全球范围内已有1.02亿例感染病例,死亡人数已攀升至221万。源自英国、巴西和南非的SARS-CoV-2变异毒株具有更高的传播率和相关死亡率。因此,迫切需要针对SARS-CoV-2的新型治疗和预防方法。虽然一些抗病毒药物,如瑞德西韦,能为某些患者群体带来缓解,但其他现有的抗病毒药物或美国食品药品监督管理局(FDA)批准的药物组合尚未显示出对新冠病毒病的临床疗效。具有强大且广泛抗病毒特性、针对呼吸道病毒有不同作用机制的化合物,可能为对抗SARS-CoV-2及其变异毒株提供新方法,特别是如果这些化合物被归类为一般认为安全(GRAS)的物质。大量证据表明,表没食子儿茶素-3-没食子酸酯(EGCG)及其衍生物有潜力作为有效药物对抗多种致病病毒感染。然而,EGCG或其衍生物尚未直接针对SARS-CoV-2进行测试。本研究旨在评估EGCG对灵长类上皮细胞中SARS-CoV-2感染的潜在抗病毒活性。该研究采用的方法包括分别使用Vero 76(绿猴上皮细胞)和Caco-2(人上皮细胞)细胞系进行细胞病变效应(CPE)测定和病毒产量降低(VYR)测定。结果表明,0.27μg/ml(0.59μM)的EGCG可使Vero 76细胞中的SARS-CoV-2感染减少50%(即半数有效浓度[EC50]=0.27μg/ml)。EGCG对Caco-2细胞中的SARS-CoV-2感染也有抑制作用,其90%有效浓度[EC90]=28μg/ml(61μM)。据我们所知,这些结果是关于EGCG对SARS-CoV-2抗病毒活性的首次观察结果,并表明在进一步的临床前和临床研究之前,EGCG及其衍生物可用于对抗新冠病毒病和其他呼吸道病毒感染引起的疾病。