ArticleThe Biochemical journal2021
Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp5 main protease.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 63 citations in OpenAlex.
- An automated positive selection screen in yeast provides support for boron-containing compounds as inhibitors of SARS-CoV-2 main protease.Microbiology spectrum · 2024Article
- Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3.Journal of virology · 2024Article
- Targeting the Main Protease (MACS chemical biology · 2024Article
- On the origins of SARS-CoV-2 main protease inhibitors.RSC medicinal chemistry · 2024Review
- Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.European journal of medicinal chemistry · 2023Review
- Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.Communications biology · 2023Article
- Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3.PLoS pathogens · 2023Article
- Targeting SARS-CoV-2 Non-Structural Proteins.International journal of molecular sciences · 2023Review
- What do we know about the function of SARS-CoV-2 proteins?Frontiers in immunology · 2023Review
- Toll-like Receptor Mediation in SARS-CoV-2: A Therapeutic Approach.International journal of molecular sciences · 2022Review
- Beyond the vaccines: a glance at the small molecule and peptide-based anti-COVID19 arsenal.Journal of biomedical science · 2022Review
- The SARS-CoV-2 main protease (MMedComm · 2022Review
- Application of Baculovirus Expression Vector system (BEV) for COVID-19 diagnostics and therapeutics: a review.Journal, genetic engineering & biotechnology · 2022Review
- Why antidiabetic drugs are potentially neuroprotective during the Sars-CoV-2 pandemic: The focus on astroglial UPR and calcium-binding proteins.Frontiers in cellular neuroscience · 2022Review
- A Review of the Current Landscape of SARS-CoV-2 Main Protease Inhibitors: Have We Hit the Bullseye Yet?International journal of molecular sciences · 2021Review
- Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp15 endoribonuclease.The Biochemical journal · 2021Article
- An all-out assault on SARS-CoV-2 replication.The Biochemical journal · 2021Article
- Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp14/nsp10 exoribonuclease.The Biochemical journal · 2021Article
- Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp12/7/8 RNA-dependent RNA polymerase.The Biochemical journal · 2021Article
- Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase.The Biochemical journal · 2021Article
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
Abstract
The coronavirus 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread around the world with unprecedented health and socio-economic effects for the global population. While different vaccines are now being made available, very few antiviral drugs have been approved. The main viral protease (nsp5) of SARS-CoV-2 provides an excellent target for antivirals, due to its essential and conserved function in the viral replication cycle. We have expressed, purified and developed assays for nsp5 protease activity. We screened the nsp5 protease against a custom chemical library of over 5000 characterised pharmaceuticals. We identified calpain inhibitor I and three different peptidyl fluoromethylketones (FMK) as inhibitors of nsp5 activity in vitro, with IC50 values in the low micromolar range. By altering the sequence of our peptidomimetic FMK inhibitors to better mimic the substrate sequence of nsp5, we generated an inhibitor with a subnanomolar IC50. Calpain inhibitor I inhibited viral infection in monkey-derived Vero E6 cells, with an EC50 in the low micromolar range. The most potent and commercially available peptidyl-FMK compound inhibited viral growth in Vero E6 cells to some extent, while our custom peptidyl FMK inhibitor offered a marked antiviral improvement.
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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.