ArticleProtein science : a publication of the Protein Society2022
Crystal structure of SARS-CoV-2 nsp10-nsp16 in complex with small molecule inhibitors, SS148 and WZ16.
Article in Protein science : a publication of the Protein Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- Hitting Coronaviruses Where It Hurts: Antiviral Strategies Targeting Viral Proteins.ChemMedChem · 2026Review
- Article
- Assay development and screening of inhibitors targeting the SARS-CoV-2 2'-O-methyltransferase NSP16.Pharmaceutical science advances · 2025Article
- Article
- Structural basis for broad-spectrum binding of AT-9010 to flaviviral methyltransferases.Archives of virology · 2025Article
- Transfer learning towards predicting viral missense mutations: A case study on SARS-CoV-2.Computational and structural biotechnology journal · 2025Article
- Structural Basis for Inhibition of the SARS-CoV-2 nsp16 by Substrate-Based Dual Site Inhibitors.ChemMedChem · 2024Article
- Perspective for Drug Discovery Targeting SARS Coronavirus Methyltransferases: Function, Structure and Inhibition.Journal of medicinal chemistry · 2024Review
- Article
- Structure-Based Virtual Screening for Methyltransferase Inhibitors of SARS-CoV-2 nsp14 and nsp16.Molecules (Basel, Switzerland) · 2024Article
- Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors.bioRxiv : the preprint server for biology · 2024Article
- SARS-CoV-2 and the DNA damage response.The Journal of general virology · 2023Review
- Coronavirus 2'-O-methyltransferase: A promising therapeutic target.Virus research · 2023Review
- Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors.ACS infectious diseases · 2023Article
- Article
- Structure-Based Discovery of Inhibitors of the SARS-CoV-2 Nsp14 N7-Methyltransferase.Journal of medicinal chemistry · 2023Article
- Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase.Nature communications · 2023Article
- SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses.Biochimica et biophysica acta. General subjects · 2023Article
- Crystal structure of SARS-CoV-2 nsp10-nsp16 in complex with small molecule inhibitors, SS148 and WZ16.Protein science : a publication of the Protein Society · 2022Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
SARS-CoV-2 nsp10-nsp16 complex is a 2'-O-methyltransferase (MTase) involved in viral RNA capping, enabling the virus to evade the immune system in humans. It has been considered a valuable target in the discovery of antiviral therapeutics, as the RNA cap formation is crucial for viral propagation. Through cross-screening of the inhibitors that we previously reported for SARS-CoV-2 nsp14 MTase activity against nsp10-nsp16 complex, we identified two compounds (SS148 and WZ16) that also inhibited nsp16 MTase activity. To further enable the chemical optimization of these two compounds towards more potent and selective dual nsp14/nsp16 MTase inhibitors, we determined the crystal structure of nsp10-nsp16 in complex with each of SS148 and WZ16. As expected, the structures revealed the binding of both compounds to S-adenosyl-L-methionine (SAM) binding pocket of nsp16. However, our structural data along with the biochemical mechanism of action determination revealed an RNA-dependent SAM-competitive pattern of inhibition for WZ16, clearly suggesting that binding of the RNA first may help the binding of some SAM competitive inhibitors. Both compounds also showed some degree of selectivity against human protein MTases, an indication of great potential for chemical optimization towards more potent and selective inhibitors of coronavirus MTases.
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