Open AccessBiochemical screening for SARS-CoV-2 main protease inhibitors
Author(s) -
Camila Coelho,
Gloria Gallo,
Cláudia Barbosa Ladeira de Campos,
Leon Hardy,
Martin Würtele
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0240079
Subject(s) - protease , proteases , chemistry , indinavir , high throughput screening , biochemistry , cysteine protease , biology , pharmacology , enzyme , virology , virus , viral load , antiretroviral therapy
The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic represents a global challenge. SARS-CoV-2's ability to replicate in host cells relies on the action of its non-structural proteins, like its main protease (M pro ). This cysteine protease acts by processing the viruses' precursor polyproteins. As proteases, together with polymerases, are main targets of antiviral drug design, we here have performed biochemical high throughput screening (HTS) with recombinantly expressed SARS-CoV-2 M pro . A fluorescent assay was used to identify inhibitors in a compound library containing known drugs, bioactive molecules and natural products. These screens led to the identification of 13 inhibitors with IC 50 values ranging from 0.2 μM to 23 μM. The screens confirmed several known SARS-CoV M pro inhibitors as inhibitors of SARS-CoV-2 M pro , such as the organo-mercuric compounds thimerosal and phenylmercuric acetate. Benzophenone derivatives could also be identified among the most potent screening hits. Additionally, Evans blue, a sulfonic acid-containing dye, could be identified as an M pro inhibitor. The obtained compounds could be of interest as lead compounds for the development of future SARS-CoV-2 drugs.