Researchers of the Zelinsky Institute participate in the development of drugs against COVID-19

The global pandemic of the new coronavirus infection COVID-19, caused by the SARS-CoV-2 virus, has spread around the world. One of the main directions in the fight against viral infections is the use of specific chemotherapeutic agents aimed at suppressing the replication of the virus in the host cell. The use of antiviral drugs at an early stage of the development of the disease can significantly reduce the viral load on the body and the development of complications caused by an infectious disease.

Scientists of the Laboratory of Supramolecular Chemistry of the ZIOC in collaboration with colleagues from the Vorozhtsov IOC SB RAS, Lomonosov Moscow State University, Altai State University, and the Vector Institute in their current research project studied a new family of inhibitors of the main viral protease SARS-CoV-2, which are derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine). In the course of the work, based on the created pharmacophore model of the protease active site, a group of compounds was modeled, which were then synthesized and tested for activity against the main SARS-CoV-2 viral protease. The results of the experiments performed with the participation of bispidine compounds showed that 14 molecules exhibit activity in the concentration range of 1–10 μM. Based on the experimental and theoretical data obtained, further directions for the development of this area of the search for effective drugs for COVID-19 are proposed.

The results of the study were put on the cover of the highly rated journal ACS Medicinal Chemistry Letters.

Source:

Dmitriy Shcherbakov, Dmitriy Baev, Mikhail Kalinin, Alexander Dalinger, Varvara Chirkova, Svetlana Belenkaya, Aleksei Khvostov, Dmitry Krut’ko, Aleksei Medved’ko, Ekaterina Volosnikova, Elena Sharlaeva, Daniil Shanshin, Tatyana Tolstikova, Olga Yarovaya, Rinat Maksyutov, Nariman Salakhutdinov, Sergey Vatsadze Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors ACS Med. Chem. Lett. 2022, 13, 140−147. DOI: 10.1021/acsmedchemlett.1c00299.