Computational and in vitro experimental analyses of the Anti-COVID-19 potential of Mortaparib and MortaparibPlus

COVID-19 pandemic caused by SARS-CoV-2 virus has become a global health emergency. Although new vaccines have been generated and being implicated, discovery application of novel preventive control measures are warranted. We aimed to identify compound/s that may possess the potential either block entry host cells or attenuate its replication upon infection. Using cell surface receptor expression (Angiotensin-converting enzyme 2 (ACE2) Transmembrane protease serine (TMPRSS2) analysis as an assay, we earlier screened several synthetic natural compounds identified candidates showed ability downregulate their expression. Here, report experimental computational analyses two small molecules, Mortaparib MortaparibPlus were initially dual inhibitors mortalin PARP-1, for activity against SARS-CoV-2. In silico MortaparibPlus, but not Mortaparib, stably binds into catalytic pocket TMPRSS2. vitro treated revealed downregulation ACE2 TMPRSS2; did show any effect. Furthermore, on main (Mpro) also predicted inhibitory MortaparibPlus. However, based anti-virus drug screening assay 30~60% viral inhibition in with non-toxic doses Mortaparib. The data suggests these closely related multimodal anti-COVID 19 activities. Whereas works through direct interactions/effects receptors (ACE2 TMPRSS2) protein (Mpro), involves independent mechanisms, elucidation which warrants further studies.