The Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious health threats to humanity and jeopardized the global economy.

However, no effective drugs are currently available to treat COVID-19 despite the great demand to fight against it.

By combining computational screening and an efficient cellular pseudotyped virus system, a research team led by Professor Yuan Shuguang from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences has confirmed that clinical histone deacetylase (HDAC) inhibitors can efficiently prevent SARS-CoV-2 and potentially be effective against COVID-19.

The researchers found that several HDAC inhibitors can bind to human angiotensin I converting enzyme 2 (ACE2) on the cell surface which in turn results in overall structural changes of ACE2. Since SARS-CoV-2 recognizes the human ACE2 receptor by its Spike protein during viral infection, such alterations inhibit ACE2-S protein binding and prevent host cell entry by SARS-CoV-2.

Inspired by this result, the team then screened 18 commercially available HDAC inhibitors and studied their efficacy in inhibiting the entry of SARS-CoV-2 into cells. They found that the four inhibitors panobinostat, givinostat hydrochloride monohydrate, CAY10603 and sirtinol are noticeably effective.

The lowest half maximal effective concentration (EC50) of viral transduction inhibition achieved by these four HDAC drugs is about 3 μM, which is far less than the EC50 obtained from other non-effective drugs (all more than 100 μM).

The possible mechanism of these HDAC inhibitors that makes them effective against SARS-CoV-2 was revealed by cellular signaling network analysis.

This work was published as a cover story in ACS Pharmacology & Translational Science.

Source: Shenzhen Institutes of Advanced Technology,

Chinese Academy of Sciences