Viruses are infectious agents that affect all living organisms, including humans. A common human virus called herpes simplex virus, or HSV, can cause cold sores, genital infections, fingertip and eye infections. When HSV infects the eye, it’s called HSV keratitis. This infection can cause visual impairment, blindness, or brain swelling.
The standard way doctors treat an HSV infection is with an antiviral drug called acyclovir. However, they’ve found this drug is no longer effective at treating some HSV infections. The infections that persist are called acyclovir-resistant infections. Therefore, scientists seek new methods to treat HSV infections.
Scientists at the Nanjing University in China examined 502 natural compounds to determine if any could be used to treat HSV keratitis. The scientists collected kidney cells from African green monkeys, treated the kidney cells with these natural compounds, and then infected them with the virus.
After 2 days, they examined the cells under a microscope to determine how much damage each compound prevented compared to untreated infected cells, called the control samples. Of all 502 compounds tested, they found the compound best at protecting cells from viral infection was present in the purple passion flower. The compound’s name is harmol, and they reported that it inhibited over 90% of HSV in the kidney cells.
The scientists further investigated the anti-HSV properties of harmol by testing whether it was toxic to the host kidney cells. If harmol is toxic to non-infected cells, it could kill the cells instead of protecting them from the virus. They tested 9 concentrations of harmol on the cells, ranging from 0 micromolar to 250 micromolar harmol. They found that the compound protected against the virus and did not kill the host cells at a concentration of 12.5 micromolar.
Then, they investigated how harmol affected the growth of the virus and the production of viral proteins and particles in the host cells. They found that harmol inhibited HSV growth and reproduction, even in acyclovir-resistant infections. The scientists also reported that harmol treatment inhibited HSV growth when added before, during, and after HSV infection. However, it was more effective the sooner it was added and most effective when added before infection.
The scientists then tested whether harmol worked in mice. They wanted to determine if harmol is safe and effective for treating live animals with HSV keratitis rather than cells alone. First, the scientists investigated whether they could safely apply harmol solution to the mice’s eyes. They applied harmol to the eyes of one group of mice and saline solution to the eyes of the control group. They examined the mice’s body weight and corneas for 5 days and found that harmol didn’t affect either when compared to mice given saline solution. They suggested this meant that harmol is a safe treatment for mice with HSV keratitis.
Next, the scientists infected 3 groups of mice with HSV. They treated the first group with acyclovir and the second group with harmol, but left the third group untreated. They administered daily harmol eyedrop treatments for 5 days and observed the mice on days 3 and 5. They reported that the harmol-treated mice fared better than the untreated mice in all characteristics they observed. Harmol-treated mice given HSV had less damage to their corneas, reduced eyelid inflammation, less weight loss, reduced corneal thickness, and higher central nerve density than untreated mice gwith HSV. They found this was true even for mice infected with acyclovir-resistant HSV.
The researchers concluded that harmol can alleviate early symptoms of HSV keratitis in mice. Therefore, they proposed that harmol may be an antiviral agent against HSV. Because harmol and acyclovir interact with acyclovir-resistant HSV differently, the scientists think the 2 compounds must inhibit HSV differently. However, they noted that one limitation of their study is that they only examined the mice for 5 days post-infection. They remarked that further researchers should explore the long-term safety and effectiveness of harmol treatment for HSV keratitis.
