MOLECULAR DOCKING STUDY REVEALS THE POTENTIAL REPURPOSING OF HISTONE DEACETYLASE INHIBITORS AGAINST COVID-19Abstract
The outburst of new coronavirus (COVID-19) infections, firstly appeared in Wuhan in 2019, has massively expanded to the whole world. At the end of March 2020, the rapid spread of the infection happened in about 206 countries around the globe. At the moment, the statistics of WHO on coronavirus pandemic revealed total infected cases of 21,770,000 and more than 77,000 deaths all over the world, with no proven antiviral agent available yet to control COVID-19 infection. The world is currently in desperate need of finding potent therapeutic agents. Histone deacetylases (HDACs) represent one of the most promising viral targets. Importantly, HDACs are critical factors involved in the control of viral replication. The molecular mechanisms associated with underlying the role of HDACs in viral latency, viral reactivation, and carcinogenesis are progressively disclosed. Till now, six HDACIs anticancer drugs have been approved by the FDA. Herein, in the in-silico structure-based drug design approach was utilized to identify novel structural characteristics for the potential repurposed activity of HDACIs as antivirals for COVID-19. In this respect, 12 HDACIs were carefully screened to probe their possible anti-viral activity against SARS-CoV main proteaseMpro (PDB: 6LU7). Most of the screened HDACIs are strongly bind into the active binding site of crystallographic structure of Mpro (PDB: 6LU7) with comparable docking energy and hydrogen bond formation. These findings demonstrate that HDACIs, especially Romidepsin and its active form (RedFK), hold promise as COVID-19 protease inhibitors. Moreover, calculations of physicochemical parameters and drug-likeness properties of the screened compounds implied an acceptable ADMET for all tested compounds.
M. F. A. Mohamed *, G. E. A. Abuo-Rahma, A. M. Hayallah, M. A. Aziz, A. Nafady and E. Samir
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag, Egypt.
28 May 2020
19 August 2020
23 August 2020
01 September 2020