The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No effective drug or vaccine is readily available. The viral RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target. A hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected market available drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC₅₀ values of 0.008μM and 9.453 μM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）病毒的传播对全球公共卫生构成了严重威胁，并导致世界范围的危机。没有有效的药物或疫苗容易获得。病毒RNA依赖性RNA聚合酶（RdRp）是有前途的治疗目标。提出了一种混合药物筛选程序，并将其用于从1906个批准的药物中识别针对RdRp的潜在候选药物。在四种选定的市场可用候选药物中，已证实普拉瑞曲酯和阿奇霉素可在体外用EC ₅₀有效抑制SARS-CoV-2复制值分别为0.008μM和9.453μM。首次，我们的研究发现，在相同的实验条件下，普拉普拉酯能有效地抑制SARS-CoV-2复制，并具有比Remdesivir更强​​的抑制活性。本文证明了对SARS-CoV-2抑制剂进行快速，准确的抗病毒药物筛选的可行性，并提供了针对COVID-19的潜在治疗剂。