ArticleMethods (San Diego, Calif.)2021
Bisindolylmaleimide IX: A novel anti-SARS-CoV2 agent targeting viral main protease 3CLpro demonstrated by virtual screening pipeline and in-vitro validation assays.
Article in Methods (San Diego, Calif.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Iron dysregulation in COVID-19 and reciprocal evolution of SARS-CoV-2: Natura nihil frustra facit.Journal of cellular biochemistry · 2022Pooled it
- Indian contribution toward biomedical research and development in COVID-19: A systematic review.Indian journal of pharmacologyPooled it
- Structure-Based Virtual Screening for Methyltransferase Inhibitors of SARS-CoV-2 nsp14 and nsp16.Molecules (Basel, Switzerland) · 2024Article
- Bisindolyl Maleimides and Indolylmaleimide Derivatives-A Review of Their Synthesis and Bioactivity.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure.International journal of molecular sciences · 2023Article
- In Silico Binding of 2-Aminocyclobutanones to SARS-CoV-2 Nsp13 Helicase and Demonstration of Antiviral Activity.International journal of molecular sciences · 2023Article
- Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus.Diabetes research and clinical practice · 2023Article
- InhibitingPharmaceuticals (Basel, Switzerland) · 2023Article
- Antiviral Potential of Plants against COVID-19 during Outbreaks-An Update.International journal of molecular sciences · 2022Review
- Protein Kinase C Inhibitors Reduce SARS-CoV-2 Replication in Cultured Cells.Microbiology spectrum · 2022Article
- New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture.Molecules (Basel, Switzerland) · 2022Article
- Novel Drug Design for Treatment of COVID-19: A Systematic Review of Preclinical Studies.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Review
- Homology Modeling,Frontiers in cellular and infection microbiology · 2022Article
- Toward interdisciplinary methods appropriate for optimal epidemic control.Methods (San Diego, Calif.) · 2021Article
- A novel compound active against SARS-CoV-2 targeting uridylate-specific endoribonuclease (NendoU/NSP15):RSC medicinal chemistry · 2021Article
- Efficiency Improvements and Discovery of New Substrates for a SARS-CoV-2 Main Protease FRET Assay.SLAS discovery : advancing life sciences R & D · 2021Article
- Antiviral evaluation of hydroxyethylamine analogs: Inhibitors of SARS-CoV-2 main protease (3CLpro), a virtual screening and simulation approach.Bioorganic & medicinal chemistry · 2021Article
- Heparin: A simplistic repurposing to prevent SARS-CoV-2 transmission in light of its in-vitro nanomolar efficacy.International journal of biological macromolecules · 2021Article
- SARS-CoV-2: from its discovery to genome structure, transcription, and replication.Cell & bioscience · 2021Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2'-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = 5903). The screening was performed against viral targets using three sequential docking modes (i.e., HTVS, SP, and XP). Virtual screening identified ∼290 potential inhibitors based on the criteria of energy, docking parameters, ligand, and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. The top lead from each target pool was further subjected to molecular dynamics simulation using the Desmond module. The resulting top eight hits were tested for their SARS-CoV-2 anti-viral activity in-vitro. Among these, a known inhibitor of protein kinase C isoforms, Bisindolylmaleimide IX (BIM IX), was found to be a potent inhibitor of SARS-CoV-2. Further, target validation through enzymatic assays confirmed 3CLpro to be the target. This is the first study that has showcased BIM IX as a COVID-19 inhibitor thereby validating our pipeline.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.