Scientists from the Novosibirsk Institute of Organic Chemistry, Volgograd State Technical University, and the Vector State Virology and Biotechnology Science Center have reported the creation of a series of compounds capable of countering cowpox and mousepox viruses. They show potential against other orthopox viruses, including monkeypox. This information was conveyed to socialbites.ca by the Ministry of Science and Higher Education of the Russian Federation.
There is strong belief that these compounds will exhibit activity against the monkeypox virus. The team notes high confidence that the agents will be effective, given the close similarity between monkeypox and variola viruses. A senior researcher explained that while direct testing on monkeypox had not yet occurred, the genetic and functional parallels suggest a positive outcome.
The researchers constructed compounds with structural similarities to natural substances such as camphor and fenchone. The mechanism appears to hinder the later stages of the virus life cycle, preventing the formation of new virions. However, details on the exact action require further study to fully elucidate the process.
Over 100 different molecules were produced in the course of the project. In cell culture experiments, most of these substances proved non-toxic and demonstrated strong activity against the vaccinia virus and cowpox and mousepox viruses. The team emphasized that a compound capable of suppressing cowpox may also be active against other orthopox viruses.
Vaccinia virus is used as a surrogate in early screenings because it is easier to handle. Substances are tested first against vaccinia, and the most active candidates undergo more extensive testing, including trials with ratpox, cowpox, and other orthopox viruses. If extended studies show strong inhibition of these viruses, the next step involves variola virus, the causative agent of smallpox, which marks a critical stage in drug development for security reasons.
At this stage, only the most well-supported compounds proceed to testing against variola. The cautious approach aims to minimize risk and ensure safety early in the development pipeline.
Thus far, experiments have been conducted in cell cultures. Before any animal testing begins, researchers must address bioavailability challenges. The newly formed molecules show poor water solubility, and finding an effective delivery method is essential to ensure the substances reach the bloodstream in adequate amounts.
Researchers also compared the antiviral activity of the new compounds with established drugs such as Cidofovir and ST-246. In cell culture, some new compounds outperformed Cidofovir but fell short of the activity shown by ST-246. This comparative insight helps guide ongoing optimization and selection of the most promising candidates.
The team notes that the development of new antiviral agents remains urgent given repeated virus threats and periodic outbreaks of diseases related to orthopox viruses. The work on antiviral agents derived from natural compounds has persisted for more than a decade, with current efforts focused on achieving superior efficacy compared with reference drugs.
A virologist commented that it is still early to draw conclusions about the potential for a smallpox drug because only a fraction of high-performing cell culture candidates translate into usable medicines. He highlighted the ongoing challenges of toxicity and specificity. Creating a compound that works at low doses, binds strongly to orthopoxvirus proteins, and avoids human or host animal proteins is a demanding task. The reality is that few candidates survive all stages of testing in animals, and several hurdles still lie ahead in determining future success.
Smallpox history underscores the severity of the disease and the importance of vaccination. Early inoculation practices date back to medieval times, while cowpox vaccination emerged in the 18th century, conferring natural immunity to smallpox. Modern vaccines emerged in the 20th century, leading to eradication declared by the World Health Organization in 1980. In May 2022, an outbreak linked to a monkeypox strain related to smallpox drew renewed attention. Transmission occurs through close contact and respiratory droplets, with cases reported in children and vulnerable populations. By early June, dozens of countries had reported infections, reflecting a growing global health concern and the need for continued vigilance in monitoring orthopox viruses.