Currently there are no effective drugs to treat coronavirus COVID-19 and there is a great need to fight it.
By combining computer screening and an efficient virus pseudotyping system, a research team led by Professor Yuan Shuguang of Shenzhen Institute of Advanced Technology (SIAT) found that clinical histone deacetylase inhibitors (HDACs), which used to treat cancer can effectively prevent SARS-CoV-2.
Researchers found that some HDAC inhibitors can bind to human angiotensin I-converting enzyme 2 (ACE2) on the cell surface, which in turn leads to general structural changes in ACE2.
Since SARS-CoV-2 recognizes the human ACE2 receptor by its spike protein during viral infection, such changes inhibit ACE2-S protein binding and prevent SARS-CoV-2 from entering host cells.
Inspired by this result, the team then screened 18 commercially available HDAC inhibitors and examined their effectiveness in inhibiting SARS-CoV-2 from entering cells.
They found that four inhibitors, namely panobinostat, givinostat hydrochloride monohydrate, CAY10603 and sirtinol, were remarkably effective.
The possible mechanism of action of these HDAC inhibitors, which makes them effective against SARS-CoV-2, has been identified by signaling network analysis.
The work was published as a cover story in ACS Pharmacology & Translational Science.