Histone deacetylase inhibitors suppress ACE2 and ABO simultaneously, suggesting a preventive potential against COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as a pandemic throughout 2020. Since the virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry, increment of ACE2 would lead to an increased risk of SARS-CoV-2 infection. At the same time, an association of the ABO blood group system with COVID-19 has also been highlighted: there is increasing evidence to suggest that non-O individuals are at higher risk of severe COVID-19 than O individuals. These findings imply that simultaneous suppression of ACE2 and ABO would be a promising approach for prevention or treatment of COVID-19. Notably, we have previously clarified that histone deacetylase inhibitors (HDACIs) are able to suppress ABO expression in vitro. Against this background, we further evaluated the effect of HDACIs on cultured epithelial cell lines, and found that HDACIs suppress both ACE2 and ABO expression simultaneously. Furthermore, the amount of ACE2 protein was shown to be decreased by one of the clinically-used HDACIs, panobinostat, which has been reported to reduce B-antigens on cell surfaces. On the basis of these findings, we conclude that panobinostat could have the potential to serve as a preventive drug against COVID-19.

2019冠状病毒病（COVID - 19）由严重急性呼吸综合征冠状病毒2（SARS - CoV - 2）引发，在2020年作为大流行病在全球传播。由于该病毒利用血管紧张素转换酶2（ACE2）作为进入细胞的受体，ACE2的增加会导致感染SARS - CoV - 2的风险增加。同时，ABO血型系统与COVID - 19的关联也受到关注：越来越多的证据表明，非O型血个体患重症COVID - 19的风险高于O型血个体。这些发现意味着同时抑制ACE2和ABO可能是预防或治疗COVID - 19的一种有前景的方法。值得注意的是，我们之前已经阐明组蛋白去乙酰化酶抑制剂（HDACIs）能够在体外抑制ABO的表达。在此背景下，我们进一步评估了HDACIs对培养的上皮细胞系的影响，发现HDACIs可同时抑制ACE2和ABO的表达。此外，一种临床使用的HDACIs——帕比司他被证明可降低ACE2蛋白的量，据报道它可减少细胞表面的B抗原。基于这些发现，我们得出结论，帕比司他有可能作为一种预防COVID - 19的药物。