A new path in the development of antivirotics: How to stop monkeypox and other viral diseases

Evžen Bouřa, Radim Nencka and their teams from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences have developed substances that could stop the monkeypox virus. The discovery was published in the prestigious scientific journal Nature Communications.

For several years, the research groups of Evžen Bouřa and Radim Nencka from the IOCB have been investigating the viral methyltransferase proteins that produce the so-called caps on RNA molecules. These caps act as a marker, which help cell to recognize its own RNA from the viral RNA. Some viruses can also form a cap, the human immune system cannot recognize them, and therefore the virus can multiply freely in the cell and cause serious infections.

We were able to elucidate the structure of the methyltransferase that forms a cap on the monkeypox virus RNA, which allowed us to design compouds that are able to bind to the methyltransferase and inhibit its function. If the function of the methyltransferase is blocked, the caps at the ends of the viral RNA are not formed and the virus is destroyed by innate immunity. The substances we have designed can also block methyltransferase in other viruses such as SARS-CoV-2 virus.

This discovery may be the first step in the development of a completely new class of antivirotics, called broad-spectrum antivirotics, which are effective against many different viruses.


Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase

Silhan, J., Klima, M., Otava, T., Skvara, P., Chalupska, D., Chalupsky, K., Kozic, J., Nencka, R., & Boura, E. (2023). Nat Commun, 14(1), 2259.

PMID: 37080993

Strange protein will help with producing antibiotics effective against resistant bacteria

Scientists from the Institute of Microbiology of the CAS, in an international collaboration with the University of Tokyo, have solved the structure of a key condensing (coupling) enzyme used for the biosynthesis of antibiotics, and clarified how it works at the molecular level. The collaborative results are so unique and significant that they were published in the June issue of the prestigious scientific journal Nature Catalysis.

Scientists from the Institute of Microbiology of the CAS in cooperation with a small Czech company Santiago Chemicals have been preparing substances effective against the dreaded staphylococcus aureus and other dangerous bacteria for several years. That’s when scientists came up with a new, more effective antibiotic called CELIN, which combines the building blocks of two natural substances – CELesticetin and LINcomycin. Since then, they have prepared dozens of derivatives, several of which are effective against antibiotic-resistant bacteria.

Currently, as part of the project of the National Institute of Virology and Bacteriology, they made another breakthrough when they and the team of Professor Ikuro Abe from the University of Tokyo elucidated the structure of the strange enzyme. This is essential for the preparation of celesticketin, a bacteriostatic antibiotic.

According to the sequence of the investigated enzymes (the sequence of amino acids in them), it was clear that they would be very different from all proteins known to date. “I was fascinated by the key condensing enzyme, it was unlike anything else. Intuition in biology tells us that it is unique systems that bring the most profound surprises and breakthroughs. I approached Professor Abe, who deals with unusual enzymes of special (secondary) metabolism of natural substances, and I agreed with him to cooperate in solving the structure and function of the condensation enzyme just published.” Jiří Janata describes the origin of the cooperation with the Japanese.


Molecular basis for carrier protein-dependent amide bond formation in the biosynthesis of lincosamide antibiotics

Mori, T., Kadlcik, S., Lyu, S., Kamenik, Z., Sakurada, K., Mazumdar, A., Wang, H., Janata, J., & Abe, I. (2023). Nature Catalysis, 1-12.

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