Zandi Keivan, Musall Katie, Oo Adrian, Cao Dongdong, Liang Bo, Hassandarvish Pouya, Lan Shuiyun, Slack Ryan L, Kirby Karen A, Bassit Leda, Amblard Franck, Kim Baek, AbuBakar Sazaly, Sarafianos Stefan G, Schinazi Raymond F
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Microorganisms. 2021 Apr 22;9(5):893. doi: 10.3390/microorganisms9050893.
Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is easily transmitted through the air and has a relatively long incubation time, COVID-19 has rapidly developed into a global pandemic. As there are no antiviral agents for the prevention and treatment of this severe pathogen except for remdesivir, development of antiviral therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein and baicalin exhibited significant antiviral activity against SARS-CoV-2, the causative agent of COVID-19 through in vitro studies. Our data through cell-based and biochemical studies showed that both compounds act as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors directly and inhibit the activity of the SARS-CoV-2 RdRp, but baicalein was more potent. We also showed specific binding of baicalein to the SARS-CoV-2 RdRp, making it a potential candidate for further studies towards therapeutic development for COVID-19 as a selective non-nucleoside polymerase inhibitor.
2019冠状病毒病（COVID-19）是一种由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的致命新发传染病。由于SARS-CoV-2易于通过空气传播且潜伏期相对较长，COVID-19已迅速发展成为全球大流行疾病。除了瑞德西韦外，目前尚无预防和治疗这种严重病原体的抗病毒药物，因此开发用于治疗感染者的抗病毒疗法仍然非常紧迫。在此，我们通过体外研究表明，黄芩素和黄芩苷对COVID-19的病原体SARS-CoV-2具有显著的抗病毒活性。我们基于细胞和生化研究的数据表明，这两种化合物均直接作为SARS-CoV-2 RNA依赖性RNA聚合酶（RdRp）抑制剂，并抑制SARS-CoV-2 RdRp的活性，但黄芩素的活性更强。我们还表明黄芩素与SARS-CoV-2 RdRp存在特异性结合，使其作为一种选择性非核苷聚合酶抑制剂，成为进一步开展COVID-19治疗开发研究的潜在候选药物。
