Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

Sulimov, Alexey; Kutov, Danil; Ilin, Ivan; Xiao, Yibei; Jiang, Sheng; Sulimov, Vladimir

doi:10.3390/molecules27092721

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Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

by

Alexey Sulimov

¹,

Danil Kutov

^1,*

,

Ivan Ilin

¹,

Yibei Xiao

²,

Sheng Jiang

² and

Vladimir Sulimov

^1,*

¹

Research Computing Center, Lomonosov Moscow State University, 119992 Moscow, Russia

²

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China

^*

Authors to whom correspondence should be addressed.

Molecules 2022, 27(9), 2721; https://doi.org/10.3390/molecules27092721

Submission received: 25 March 2022 / Revised: 17 April 2022 / Accepted: 20 April 2022 / Published: 23 April 2022

(This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research 3.0)

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Abstract

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.

Keywords: SARS-CoV-2; nsp16 inhibitor; docking; quantum chemistry; virtual screening

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MDPI and ACS Style

Sulimov, A.; Kutov, D.; Ilin, I.; Xiao, Y.; Jiang, S.; Sulimov, V. Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus. Molecules 2022, 27, 2721. https://doi.org/10.3390/molecules27092721

AMA Style

Sulimov A, Kutov D, Ilin I, Xiao Y, Jiang S, Sulimov V. Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus. Molecules. 2022; 27(9):2721. https://doi.org/10.3390/molecules27092721

Chicago/Turabian Style

Sulimov, Alexey, Danil Kutov, Ivan Ilin, Yibei Xiao, Sheng Jiang, and Vladimir Sulimov. 2022. "Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus" Molecules 27, no. 9: 2721. https://doi.org/10.3390/molecules27092721

APA Style

Sulimov, A., Kutov, D., Ilin, I., Xiao, Y., Jiang, S., & Sulimov, V. (2022). Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus. Molecules, 27(9), 2721. https://doi.org/10.3390/molecules27092721

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Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

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