Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel member of the genus betacoronavirus in the Coronaviridae family. It has been identified as the causative agent of coronavirus disease 2019 (COVID-19), spreading rapidly in Asia, America and Europe. Like some other RNA viruses, RNA replication and transcription of SARS-CoV-2 rely on its RNA-dependent RNA polymerase (RdRP), which is a therapeutic target of clinical importance. Crystal structure of SARS-CoV-2 was solved recently (PDB ID 6M71) with some missing residues.

Objective: We used SARS-CoV-2 RdRP as a target protein to screen for possible chemical molecules with potential anti-viral effects.

Methods: Here we modelled the missing residues 896-905 via homology modelling and then analysed the interactions of Hepatitis C virus allosteric non-nucleoside inhibitors (NNIs) in the reported NNIs binding sites in SARS-CoV-2 RdRP.

Results: We found that MK-3281, filibuvir, setrobuvir and dasabuvir might be able to inhibit SARS-CoV-2 RdRP based on their binding affinities in the respective binding sites.

Conclusion: Further in vitro and in vivo experimental research will be carried out to evaluate their effectiveness in COVID-19 treatment in the near future.

背景：严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 是冠状病毒科β冠状病毒属的新成员。它已被确定为 2019 年冠状病毒病 (COVID-19) 的病原体，并在亚洲、美洲和欧洲迅速传播。与其他一些 RNA 病毒一样，SARS-CoV-2 的 RNA 复制和转录依赖于其 RNA 依赖性 RNA 聚合酶 (RdRP)，这是具有临床重要性的治疗靶点。最近解析了 SARS-CoV-2 的晶体结构 (PDB ID 6M71)，其中缺少一些残基。

目的：我们使用 SARS-CoV-2 RdRP 作为靶蛋白来筛选可能具有潜在抗病毒作用的化学分子。

方法：在这里，我们通过同源建模对缺失的残基 896-905 进行建模，然后分析了丙型肝炎病毒变构非核苷抑制剂 (NNI) 在 SARS-CoV-2 RdRP 中报告的 NNI 结合位点中的相互作用。

结果：我们发现 MK-3281、filibuvir、setrobuvir 和 dasabuvir 基于它们在各自结合位点的结合亲和力可能能够抑制 SARS-CoV-2 RdRP。

结论：将在不久的将来进行进一步的体外和体内实验研究，以评估其在 COVID-19 治疗中的有效性。