Natural products with potential efficacy against deadly viruses

Researchers at the Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, have broken down the genomic and life history properties of three classes of viruses that caused endemic and global pandemics in the past and identified natural products – compounds produced in nature – with the potential to disrupt their distribution.

In a review published 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 trait that helps them develop rapidly. The team then describes the natural products that are shown to have the ability to inhibit them, and highlights possible treatment strategies.

“We wanted to evaluate the viruses responsible for these deadly outbreaks and identify their vulnerabilities,” said Christy, the first author. “We look at their similarities and reveal possible strategies to target their replication and spread. We find that natural products are a valuable source of inhibitors that can be used as a basis for new drug development campaigns targeting these viruses.”

The research team is from Scripps Oceanography’s Center for Marine Biotechnology and Biomedicine (CMBB), which collects and analyzes chemical compounds found in marine environments for potential efficacy as antibiotics, cancer treatments and other products with medical benefit. A drug known as Marizomib entered the final phase of clinical trials earlier in 2020 as a possible treatment for brain cancer. The drug is derived from a type of marine bacteria that CMBB researchers originally collected in seabed sediments in 1990.

The researchers, funded by the National Institutes of Health and the UC San Diego Chancellor’s Office, provide an overview of the structure of viruses in the families Coronaviridae, Flaviviridae and Filoviridae. Within these families are viruses that have led to COVID-19, dengue fever, West Nile encephalitis, Zika, Ebola and Marburg disease. The team then identifies compounds produced by marine and terrestrial organisms that show some activity against these viruses. These compounds are believed to have molecular architectures that could serve as potential candidates to act as virus inhibitors, preventing viruses from entering or repeating healthy human cells. The researchers said the aim of the review was to improve the process of drug development as new pandemics emerge so that the spread of diseases can accelerate in the face of new threats.

“It is simply common sense that we need to put in place the necessary infrastructure to develop treatments faster when future pandemics occur”, the review concludes. “One such recommendation is to create and maintain international composite libraries with substances that have antiviral, antibacterial or antiparasitic activity.”

To achieve this goal, the researchers realize that international agreements need to be reached 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 critically needed for the treatment of COVID-19 infection in individuals who have not been vaccinated, or in cases where the efficacy of a vaccine decreases over time, researchers said. While several candidate antiviral molecules have been investigated for use in the clinic, such as inhibitor, lopinavir-ritonavir, hydroxychloroquine, and type I interferon therapy, all have shown limited or no efficacy in large-scale trials. Effective antiviral drugs still have a great need for discovery and development.