Novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagation. In this study, siRNA-mediated silencing of Pin1 expression markedly suppressed the proliferation of SARS-CoV-2 in VeroE6/TMPRSS2 cells. In addition, several recently generated Pin1 inhibitors showed strong inhibitory effects on SARS-CoV-2 proliferation, measured by both viral mRNA and protein synthesis, and alleviated the cytopathic effect (CPE) on VeroE6/TMPRSS2 cells. One compound, termed H-77, was found to block SARS-CoV-2 proliferation at an EC₅₀ below 5 μM regardless of whether it was added to the culture medium prior to or after SARS-CoV-2 infection. The inhibition of viral N protein mRNA synthesis by H-77 implies that the molecular mechanism underlying SARS-CoV-2 inhibition is likely to be associated with viral gene transcription or earlier steps. Another Pin1 inhibitor, all-trans retinoic acid (ATRA)—a commercially available drug used to treat acute promyelocytic leukemia (APL) and which both activates the retinoic acid receptor and inhibits the activity of Pin1—similarly reduced the proliferation of SARS-CoV-2. Taken together, the results indicate that Pin1 inhibitors could serve as potential therapeutic agents for COVID-19.

2019 年新型冠状病毒病 (COVID-19) 已成为具有深远社会影响的全球大流行病。在这里，我们证明 Pin1 是严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 传播所必需的关键细胞分子。在这项研究中，siRNA 介导的 Pin1 表达沉默显着抑制了 SARS-CoV-2 在 VeroE6/TMPRSS2 细胞中的增殖。此外，最近产生的几种 Pin1 抑制剂对 SARS-CoV-2 增殖显示出强烈的抑制作用，通过病毒 mRNA 和蛋白质合成来衡量，并减轻了对 VeroE6/TMPRSS2 细胞的细胞病变效应（CPE）。发现一种名为 H-77 的化合物在 EC _{50 时}阻止 SARS-CoV-2 增殖无论是在 SARS-CoV-2 感染之前还是之后将其添加到培养基中，均低于 5 μM。H-77 对病毒 N 蛋白 mRNA 合成的抑制意味着 SARS-CoV-2 抑制的分子机制可能与病毒基因转录或更早的步骤有关。另一种 Pin1 抑制剂，全反式视黄酸 (ATRA)——一种用于治疗急性早幼粒细胞白血病 (APL) 的市售药物，它既能激活视黄酸受体，又能抑制 Pin1 的活性——同样降低了 SARS-CoV 的增殖—— 2. 总之，结果表明 Pin1 抑制剂可以作为 COVID-19 的潜在治疗剂。