The recent outbreak of coronavirus disease 2019 (COVID-19) by SARS-CoV-2 has led to uptodate 24.3 M cases and 0.8 M deaths. It is thus in urgent need to rationalize potential therapeutic targets against the progression of diseases. An effective, feasible way is to use the pre-existing ΔORF6 mutant of SARS-CoV as a surrogate for SARS-CoV-2, since both lack the moiety responsible for interferon antagonistic effects. By analyzing temporal profiles of upregulated genes in ΔORF6-infected Calu-3 cells, we prioritized 55 genes and 238 ligands to reposition currently available medications for COVID-19 therapy. Eight of them are already in clinical trials, including dexamethasone, ritonavir, baricitinib, tofacitinib, naproxen, budesonide, ciclesonide and formoterol. We also pinpointed 16 drug groups from the Anatomical Therapeutic Chemical classification system, with the potential to mitigate symptoms of SARS-CoV-2 infection and thus to be repositioned for COVID-19 therapy.

最近由 SARS-CoV-2 爆发的 2019 年冠状病毒病 (COVID-19) 已导致最新 2430 万例病例和 0.8 百万例死亡。因此，迫切需要合理化针对疾病进展的潜在治疗靶点。一种有效、可行的方法是使用 SARS-CoV 的预先存在的 ΔORF6 突变体作为 SARS-CoV-2 的替代物，因为两者都缺乏负责干扰素拮抗作用的部分。通过分析 ΔORF6 感染的 Calu-3 细胞中上调基因的时间分布，我们优先考虑 55 个基因和 238 个配体，以重新定位目前可用的 COVID-19 治疗药物。其中八种已经在临床试验中，包括地塞米松、利托那韦、巴瑞克替尼、托法替尼、萘普生、布地奈德、环索奈德和福莫特罗。