Natural products with potential effectiveness against lethal viruses

Researchers at the Scripps Institution of Oceanography and the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego analyzed the genomic and life history characteristics of three classes of viruses that have caused endemic and global pandemics in the past and identified natural products— compounds produced in nature – with the potential to stop its spread.

In a review that appears in the Journal of Natural Products, marine chemists Mitchell Christy, Yoshinori Uekusa and William Gerwick and immunologist Lena Gerwick describe the basic biology of three families of RNA viruses and how they infect human cells. These viruses use RNA instead of DNA to store their genetic information, a feature that helps them to evolve quickly. The team then describes the natural products that have been shown to have the resources to inhibit them, highlighting possible treatment strategies.

“We wanted to assess the viruses that are responsible for these deadly outbreaks and identify their weaknesses,” said Christy, the first author. “We consider their similarities and reveal potential strategies to target their replication and spread. We have found that natural products are a valuable source of inhibitors that can be used as the basis for new drug development campaigns targeting these viruses.”

The research team is from the Oceanography Scripps Center for Marine Biotechnology and Biomedicine (CMBB), which collects and analyzes chemical compounds found in marine environments for potential effectiveness such as antibiotics, anticancer therapies and other products with medical benefit. A drug known as Marizomib entered the final stages of clinical testing as a potential treatment for brain cancers in early 2020. The drug came from a genus of marine bacteria that CMBB researchers originally collected from seabed sediments in 1990.

The researchers, funded by the National Institutes of Health and UC San Diego Chancellor’s Office, provide an overview of the structure of viruses in the Coronaviridae, Flaviviridae and Filoviridae families. Within these families are the viruses that caused outbreaks of COVID-19, dengue, West Nile encephalitis, Zika, Ebola and Marburg diseases. The team then identifies compounds produced by marine and terrestrial organisms that have some demonstrated level of activity against these viruses. These compounds are believed to have molecular architectures that make them potential candidates to serve as viral inhibitors, preventing viruses from entering healthy human cells or replicating. The purpose of the review, the researchers said, is to improve the drug development process as new pandemics emerge, so that curbing the spread of the disease can be accelerated in the face of new threats.

“It is simply common sense that we should put in place the necessary infrastructure to develop treatments more quickly when future pandemics occur,” concludes the review. “One of those recommendations is to create and maintain international libraries of compounds with substances that have antiviral, antibacterial or antiparasitic activity.”

To achieve this goal, researchers realize that it would be necessary to reach international agreements to address issues of intellectual property, the rights and responsibilities of researchers and other complex issues.

And although there has been remarkable progress in the development of vaccines for SARS-CoV-2 infection, effective antiviral drugs are also extremely necessary for the control of COVID-19 infection in unvaccinated individuals or in cases where the effectiveness of a vaccine decreases over time, the researchers said. Although several candidate antiviral molecules have been investigated for clinical use, such as remdesivir, lopinavir-ritonavir, hydroxychloroquine and type I interferon therapy, all have shown limited or no efficacy in large-scale trials. Effective antiviral drugs have yet to be discovered and developed.