The study identifies potent SARS-CoV-2 inhibitors which could serve as a valuable starting point for further investigations

The Covid-19 pandemic is one of the greatest challenges modern medicine has ever faced. While repurposing studies of existing drugs haven’t shown very promising results, there is an urgent need to find new approaches and medicines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Tackling this problem, a team led by Prof. Kristaps Jaudzems (IOS, Laboratory of Physical Organic Chemistry) has investigated an approach to inhibit viral mRNA cap methyltransferases (MTases) which are emerging targets for the development of broad-spectrum antiviral agents. This study is accepted for publication in the ACS Medicinal Chemistry Letters (IF= 3.975).

Researchers have designed and synthesized compounds that show nanomolar to submicromolar potency against SARS-CoV-2 mRNA cap MTases Nsp14 and Nsp16. Studying the selectivity of the identified compounds, they appear to be nonselective to human GNMT and have poor cell permeability.

Nevertheless this research will warranty further studies to identify novel antiviral agents with appropriate properties and selectivity toward coronavirus MTases. The availability of the crystal structures of Nsp14, Nsp16, and human GNMT will allow a structure-guided approach to perform further design of new compounds.

Read the article:

Bobiļeva, O.; Bobrovs, R.; Kaņepe, I.; Patetko, L.; Kalniņš, G.; Šišovs, M.; Bula,A.L.; Grīnberga, S.; Borodušķis, M.; Ramata-Stunda, A.; Rostoks, N.; Jirgensons, A.; Tārs, K.; Jaudzems, K.*
Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate.
ACS Med. Chem. Lett., 2021. DOI: 10.1021/acsmedchemlett.1c00140

This work was supported by the Latvian Council of Science (grant No. VPP-COVID-2020/1–0014).