Entrectinib—A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells

Abstract

Since the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a potential antiviral drug.

Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT

“…It is important to mention that the magnitude of depends on the conformational state of the protein ( Chalikian and Filfil, 2003 ). These volumetric results at 100 ns are in agreement with the results obtained by molecular simulations using Anisotropic Network models (ANM) and Gaussian Network Model (GNM) ( Alvarado et al, 2015 , Peralta-Garcia et al, 2021 ). In the ANM and GNM, if the number of flexible fragments of a protein-ligand complex is higher than in the respective uncomplexed protein in its native state, it is interpreted that an unfolding induced by the ligand occurred, otherwise, if they decrease in protein-ligand complex in relation to the protein without ligand binding, compaction or refolding is said to have occurred ( Alvarado et al, 2015 , Peralta-Garcia et al, 2021 ).…”

“…The values of are of higher magnitude and have a different trend than the values of revealing the important contribution that the fluctuation of the hydration layer has in and does not contribute in . An interesting result was obtained by estimating the number of flexible fragments of each biomolecule between 0 and 100 ns (see Fig.9 ) using ANM+GNM methods ( Alvarado et al, 2015 , Peralta-Garcia et al, 2021 ). The values obtained for the fluctuation of the number of flexible fragments with these data had the same trend [mM pro -B1b (1.42) > mM pro -B1a (1.27) > mM pro (1.23) > mM pro -PF (0.84)] as that obtained for the fluctuation of the Voronoi volume .…”

“…For the prediction of the number of flexible fragments ( ), HingeProt was used, a web server to predict rigid protein parts and the flexible hinge regions that connect them in the native protein chain topology using elastic network models (EN). HingeProt uses Gaussian lattice models (GNM) and anisotropic lattice models (ANM) ( http://bioinfo3d.cs.tau.ac.il/HingeProt/ ) ( Alvarado et al, 2015 , Peralta-Garcia et al, 2021 ).…”

Chalcone-amide, a privileged backbone for the design and development of selective SARS-CoV/SARS-CoV-2 papain-like protease inhibitors

“…In particular, the presence of this scaffold in the structure of HIV-1 integrase inhibitors has been repeatedly observed [ 35 , 36 ]. Entrectinib (compound 25 ) is an FDA-approved anti-cancer drug recently proposed by Garcia and co-workers as a SARS-CoV-2 inhibitor in human lung tissue cells [ 37 ].

Fig.

…”

Thyroid Cancer and COVID-19: Prospects for Therapeutic Approaches and Drug Development

“…Peralta-Garcia et al. reported the antiviral activity of entrectinib against SARS-CoV-2 in human lung tissue and in an antiviral assay involving human lung tissue cells ( 70 ).…”