Dataset Information

Discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 via virtual screening and biochemical evaluation.

ABSTRACT: SARS-CoV-2 is the pathogen that caused the global COVID-19 outbreak in 2020. Promising progress has been made in developing vaccines and antiviral drugs. Antivirals medicines are necessary complements of vaccines for post-infection treatment. The main protease (Mpro) is an extremely important protease in the reproduction process of coronaviruses which cleaves pp1ab over more than 11 cleavage sites. In this work, two active main protease inhibitors were found via docking-based virtual screening and bioassay. The IC₅₀ of compound VS10 was 0.20 μM, and the IC₅₀ of compound VS12 was 1.89 μM. The finding in this work can be helpful to understand the interactions of main protease and inhibitors. The active candidates could be potential lead compounds for future drug design.

SUBMITTER: Guo S

PROVIDER: S-EPMC7903152 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 via virtual screening and biochemical evaluation.

Guo Sheng S Xie Hang H Lei Yu Y Liu Bin B Zhang Li L Xu Yechun Y Zuo Zhili Z

Bioorganic chemistry 20210224

SARS-CoV-2 is the pathogen that caused the global COVID-19 outbreak in 2020. Promising progress has been made in developing vaccines and antiviral drugs. Antivirals medicines are necessary complements of vaccines for post-infection treatment. The main protease (Mpro) is an extremely important protease in the reproduction process of coronaviruses which cleaves pp1ab over more than 11 cleavage sites. In this work, two active main protease inhibitors were found via docking-based virtual screening a ...[more]

PMID: 33667900

Similar Datasets

Project description:Background: Due to the constant mutation of virus and the lack of specific therapeutic drugs, the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still poses a huge threat to the health of people, especially those with underlying diseases. Therefore, drug discovery against the SARS-CoV-2 remains of great significance. Methods: With the main protease of virus as the inhibitor target, 9,614 genistein derivatives were virtually screened by LeDock and AutoDock Vina, and the top 20 compounds with highest normalized scores were obtained. Molecular dynamics simulations were carried out for studying interactions between these 20 compounds and the target protein. The drug-like properties, activity, and ADMET of these compounds were also evaluated by DruLiTo software or online server. Results: Twenty compounds, including compound 11, were screened by normalized molecular docking, which could bind to the target through multiple non-bonding interactions. Molecular dynamics simulation results showed that compounds 2, 4, 5, 11, 13, 14, 17, and 18 had the best binding force with the target protein of SARS-CoV-2, and the absolute values of binding free energies all exceeded 50 kJ/mol. The drug-likeness properties indicated that a variety of compounds including compound 11 were worthy of further study. The results of bioactivity score prediction found that compounds 11 and 12 had high inhibitory activities against protease, which indicated that these two compounds had the potential to be further developed as COVID-19 inhibitors. Finally, compound 11 showed excellent predictive ADMET properties including high absorption and low toxicity. Conclusion: These in silico work results show that the preferred compound 11 (ZINC000111282222), which exhibited strong binding to SARS-CoV-2 main protease, acceptable drug-like properties, protease inhibitory activity and ADMET properties, has great promise for further research as a potential therapeutic agent against COVID-19.

Dataset Information

Discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 via virtual screening and biochemical evaluation.

Publications

Discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 via virtual screening and biochemical evaluation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets