This small therapeutic molecule treats DNA and RNA virus infections, including the herpes simplex virus (HSV) and SARS-CoV-2, with limited host cell cytotoxicity. The herpes simplex virus type 1 (HSV-1) is common and presents in approximately 90% of the population worldwide. While the clinical expression of the virus varies, HSV carriers risk developing herpes labialis, known as cold sores. Cold sores have an average incidence of 1.6 per 1,000 patients per year, and approximately one-third of all infected patients experience relapse. In addition, HSV-1 can cause herpes stromal keratitis, the leading cause of infectious blindness in the US.
Using natural products to identify initial hit compounds is a well-established strategy for drug discovery. Currently, the available approved and investigational therapeutics are mostly either repurposed or synthetic agents targeting viral proteins such as protease or RNA polymerase inhibition. Despite the availability of a few compounds possessing activity to both DNA and RNA viruses, there is still an urgent need for better options for treating viral infections that are not prone to selection toward drug resistance, and that possess potent and selective activity, and low cell toxicity. Alkaloids, isolated from various members of the Amaryllidaceae plant family, demonstrate potent anticancer, anti-viral, and acetylcholinesterase activity have not been exploited for treating viruses due to their tendency to have unfavorable toxicity profiles.
Researchers at the University of Florida have discovered a truncated ring-A Amaryllidaceae alkaloid for treating herpes simplex virus type 1 (HSV-1) and SARS-CoV-2. The small molecule has broad-spectrum anti-viral activity due to activation of synergistic defenses in the host cell, such as autophagy and upregulation of TP53. There is no viral resistance to the compound, and it has more potent anti-viral activity than present natural and synthetic alkaloids. There is potential for applying this to other herpes pathogens and, eventually, treatment for different viruses, such as the Zika virus (ZIKV).
An anti-viral agent with potent and selective anti-viral activity, targeting herpes simplex virus type 1 (HSV-1) and SARS-CoV-2
This small anti-viral molecule activates the host cell’s defense by upregulating its integrated stress response pathway. The stimulation of IFN-1 activates cell innate immunity, resulting in a broad host-cell increase of anti-viral defense, which does not depend on the host cell interacting with the highly mutable viral structural proteins. The upregulation of the host cell defense machinery to viral infection sets the standard for developing a broad-spectrum anti-viral agent with little selection toward drug resistance.