protease inhibitors (3clpro inhibitor)  (FUJIFILM)

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: Genetic material (RNA) of SARS-CoV-2 enters the host cell and borrows ribosome to translate into 16 nonstructural proteins upon auto-proteolytic cleavage by PLpro and 3CLpro enzymes. Structural proteins (S, E, M, and N) are translated by sg translation mechanism. All mature proteins assemble along with positive-sense single stranded RNA genome to form new virion. Arrows indicates the protease cleavage sites. ORF open reading frame, PLP papain like protease, 3CLP 3-chymotrypsin like protease, S spike protein, E envelop protein, M membrane protein, N nucleocaspid protein.

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques:

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: List of all the drugs with highest S score for 3CL protease calculated by computational studies (S score).

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques: Binding Assay

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: The selected FDA approved viral-protease inhibitors were screened for their inhibitory activity against SARS-CoV-2 3CLpro enzyme as described under Methods section. The fluorescence units were converted to percent enzymatic activity considering DMSO treated control as 100% activity. Blank values were subtracted from all the readings before calculating the percent activity. Representative of three individual experiments with triplicate values were presented graphically ( n = 3). P value < 0.001 considered as statistically significant. One-way ANOVA with Dunnett’s Multiple Comparison post-hoc test was used to calculate the statistical significance.

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques: Activity Assay, Fluorescence

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: The non-protease anti-viral drugs selected by computational studies were screened for their inhibitory activity against SARS-CoV-2 3CLpro enzyme as described under Methods section. The percent enzymatic activity was calculated as described in Fig. legend. Blank values were subtracted from all the readings before calculating the percent activity. Representative of three individual experiments with triplicate values were presented graphically ( n = 3). P value < 0.001 considered as statistically significant. One-way ANOVA with Dunnett’s Multiple Comparison post-hoc test used to calculate the statistical significance.

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques: Activity Assay

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: The off-target drugs that are being used to treat non-viral ailments selected by in silico studies were screened for their inhibitory activity against SARS-CoV-2 3CLpro enzyme as described under Methods section. The percent enzymatic activity was calculated as described in Fig. legend. Blank values were subtracted from all the readings before calculating the percent activity. Representative of three individual experiments with triplicate values were presented graphically ( n = 3). P value < 0.001 considered as statistically significant. One-way ANOVA with Dunnett’s Multiple Comparison post-hoc test used to calculate the statistical significance.

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques: In Silico, Activity Assay

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: Inhibitors were docked with active site of 3CLpro protein. Panel-I: ligand interaction map. Panel-II: interaction of inhibitors specific amino acids of 3CLpro at active site. Panel-III: lipophilic cavity of active site with drugs interacting with specific amino acids. Boceprevir ( a ), partapravir ( b ), tipranavir ( c ), ombitasvir ( d ), ivermectin ( e ), and micafungin ( f ) are arranged in columns for comparison. Drugs are represented in green color with ball and stick model. Arrows indicate the C–H, N–H, and C–O bonds between drugs and with Cys 145 , His 41 , and Glu 166 residues since they are essential for the enzymatic activity of 3CLpro enzyme. However, we also observed the drugs interacting with neighboring amino acid residues.

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques: Activity Assay

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: MD simulation studies were carried as described under Methods section. Interaction of micafungin ( a ), and ivermectin ( b ) with monomeric form of 3 CLpro enzyme. c Interaction of ivermectin with active site of 3CLpro homodimer. Panel I–III represents the interaction of ligand at different time points in nano second (ns). Panel-IV represents the ligand-binding fingerprint of micafungin and ivermectin with specific amino acids of 3CLpro enzymes.

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques: Ligand Binding Assay

Journal: Communications Biology

Article Title: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

doi: 10.1038/s42003-020-01577-x

Figure Lengend Snippet: Hypothetical model illustrating the inhibition of SARS-CoV-2 replication by ivermectin mediated through the blocking of α/β1-importin (imp) as well as 3CLpro enzymatic activity.

Article Snippet: 3CLpro inhibitor screening enzymatic assay kits (Catalog #79955-1) were from BPS Biosciences (San Diego, CA, USA).

Techniques: Inhibition, Blocking Assay, Activity Assay

Journal: Advanced Therapeutics

Article Title: Repurposed Drugs, Molecular Vaccines, Immune‐Modulators, and Nanotherapeutics to Treat and Prevent COVID‐19 Associated with SARS‐CoV‐2, a Deadly Nanovector

doi: 10.1002/adtp.202000172

Figure Lengend Snippet: List of potential therapeutic molecules under consideration for COVID‐19

Article Snippet: Lopinavir and ritonavir , Antiretrovirals , Protease inhibitors (3CLpro inhibitor) , Fujifilm Toyama Chemical's , Phase 0 ChiCTR2000029308 , HIV, SARS‐CoV and MERS‐CoV , [ , , , ] .

Techniques: Reflux, Membrane, Recombinant, Vaccines, Plasmid Preparation, Virus, Purification, Modification, Genetically Modified, Expressing, Adjuvant, Bioprocessing