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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. Author summary: Currently, a novel coronavirus called SARS-COV-2 is spreading across many parts of the world. Unfortunately, there is still a lack of effective drugs against the virus. Additionally, it usually takes much longer time to develop a new drug using traditional methods. Thus, it is now better to rely on some alternative methods to develop drugs that can treat such a disease effectively. In this paper, we have proposed a deep learning and molecular dynamics simulation based hybrid drug screening procedure for identifying potential drug candidates targeting RdRp from 1906 market available drugs. Our screening have successfully identified a FDA-approved drug called Pralatrexate that strongly inhibits the replication of 2019-nCoV in vitro with EC50 values of 0.008μM. This work demonstrated the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19. [ABSTRACT FROM AUTHOR]