Russian Scientists Synthesize Novel Organic Molecules to Combat Orthopoxviruses

Laboratory research. Archival photo.

Russian researchers have successfully synthesized a novel class of organic molecules designed to counteract orthopoxviruses, a family that includes the smallpox virus. These newly developed compounds hold the potential to form the basis of innovative pharmaceutical treatments. This significant achievement was announced by the Russian Science Foundation (RSF).

Current medications for smallpox often exhibit insufficient efficacy against certain strains and can lead to severe side effects, notably impacting kidney function. Consequently, the scientific community is actively seeking safer and more effective alternatives.

A team of scientists from Tomsk Polytechnic University (TPU), in collaboration with colleagues, successfully synthesized organic compounds capable of inhibiting a key protein essential for orthopoxviruses to replicate and form new viral particles. Aryloxadiazoles – cyclic molecules containing nitrogen and oxygen – were chosen as the initial platform for synthesis, as earlier studies had shown them to possess antiviral activity, albeit modest. The scientists modified these initial compounds by attaching additional chemical groups containing nitrogen, chlorine, bromine, iodine, and fluorine atoms. In total, 21 novel molecules were created.

Experiments demonstrated that 19 of these new class of compounds exhibited pronounced antiviral activity. Remarkably, five of them were effective in preventing pathogen proliferation at concentrations hundreds, and even thousands, of times lower than the therapeutic doses of cidofovir, an antiviral drug currently used in clinical practice. This high efficacy was coupled with minimal toxicity to living cells.

Artem Semenov, a research engineer at TPU`s International Research Laboratory “Non-covalent Interactions in Materials Chemistry” and a participant in the RSF-funded project, stated: “We have developed an innovative molecular platform for designing antiviral agents. This platform can be utilized to discover treatments for a wide range of pathogens, not just orthopoxviruses. Thus, our research contributes significantly to the search for new methods of preventing and treating viral infections and averting future epidemics. Our future plans involve investigating the activity of these compounds in laboratory animals, analyzing their pharmacokinetics, and more thoroughly establishing their mechanism of action.”

This multifaceted study involved specialists from various Russian scientific institutions, including Saint Petersburg State University (Saint Petersburg), K.D. Ushinsky Yaroslavl State Pedagogical University (Yaroslavl), State Research Center of Virology and Biotechnology “Vector” (Koltsovo), Ufa Federal Research Center (Ufa), Novosibirsk State University (Novosibirsk), and N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS (Novosibirsk), as well as scientists from the independent theoretical group “Quanta and Dynamics.”