7DJR

Crystal structure of SARS-CoV-2 main protease (no ligand)

Summary for 7DJR

• Entry DOI: 10.2210/pdb7djr/pdb
• Descriptor: 3C-like proteinase, DIMETHYL SULFOXIDE (3 entities in total)
• Functional Keywords: sars-cov-2, protease, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 34138.08

Authors

Deetanya, P.,Wangkanont, K. (deposition date: 2020-11-21, release date: 2021-06-16, Last modification date: 2023-11-29)

Primary citation

Deetanya, P.,Hengphasatporn, K.,Wilasluck, P.,Shigeta, Y.,Rungrotmongkol, T.,Wangkanont, K.
Interaction of 8-anilinonaphthalene-1-sulfonate with SARS-CoV-2 main protease and its application as a fluorescent probe for inhibitor identification.
Comput Struct Biotechnol J, 19:3364-3371, 2021

PubMed Abstract: The 3C-like main protease of SARS-CoV-2 (3CL) is responsible for the cleavage of the viral polyprotein. This process is essential for the viral life cycle. Therefore, 3CL is a promising target to develop antiviral drugs for COVID-19 prevention and treatment. Traditional enzymatic assays for the identification of 3CL inhibitors rely on peptide-based colorimetric or fluorogenic substrates. However, the COVID-19 pandemic has limit or delay access to these substrates, especially for researchers in developing countries attempting to screen natural product libraries. We explored the use of the fluorescent probe 8-anilinonaphthalene-1-sulfonate (ANS) as an alternative assay for inhibitor identification. Fluorescence enhancement upon binding of ANS to 3CL was observed, and this interaction was competitive with a peptide substrate. The utility of ANS-based competitive binding assay to identify 3CL inhibitors was demonstrated with the flavonoid natural products baicalein and rutin. The molecular nature of ANS and rutin interaction with 3CL was explored with molecular modeling. Our results suggested that ANS could be employed in a competitive binding assay to facilitate the identification of novel SARS-CoV-2 antiviral compounds.

PubMed: 34109016
DOI: 10.1016/j.csbj.2021.05.053

Experimental method

X-RAY DIFFRACTION (1.45 Å)