Tribenoside

Hemorrhoids are a common anorectal disease that causes pain, itching, and burning. The prevalence of hemorrhoids is estimated to be as high as 36% in the general population, with approximately 50% of individuals experiencing symptomatic hemorrhoids at least once in their life. Middle age, obesity, and pregnancy are risk factors. The combination of tribenoside and lidocaine (Procto-Glyvenol©, Recordati) has been used for decades to treat low-grade hemorrhoids, and its efficacy and safety are well supported by clinical experience. Tribenoside has been shown to have an anti-inflammatory effect, ameliorate the local microcirculation and vascular tone, and promote the healing of basement membrane. However, the molecular mechanism behind its wound-healing properties is still unclear.

Human dermal fibroblasts were used to test the effect of tribenoside on cell proliferation, cell migration, and production of reactive oxygen species in vitro. Full-thickness excisional wound model in rats was used to test the wound-healing properties of Procto-Glyvenol© in vivo.

Tribenoside has been found to increase the migration rate of fibroblasts in vitro and to improve the wound healing process by promoting re-epithelialization in rats. Furthermore, novel antioxidant activity of tribenoside has been reported, which may represent a further mechanism of action in wound healing.

Procto-Glyvenol© improves the natural healing process of wounds by stimulating cell migration and protecting against the toxic effects of reactive oxygen species. Therefore, it may represent a first-line treatment for hemorrhoids, which are a significant medical and socioeconomic problem that can deteriorate the quality of life.

We established a split nanoluciferase complementation assay to rapidly screen for inhibitors that interfere with binding of the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein with its target receptor, angiotensin-converting enzyme 2 (ACE2). After a screen of 1,200 US Food and Drug Administration (FDA)-approved compounds, we identified bifonazole, an imidazole-based antifungal agent, as a competitive inhibitor of RBD-ACE2 binding. Mechanistically, bifonazole binds ACE2 around residue K353, which prevents association with the RBD, affecting entry and replication of spike-pseudotyped viruses as well as native SARS-CoV-2 and its variants of concern (VOCs). Intranasal administration of bifonazole reduces lethality in K18-hACE2 mice challenged with vesicular stomatitis virus (VSV)-spike by 40%, with a similar benefit after live SARS-CoV-2 challenge. Our screen identified an antiviral agent that is effective against SARS-CoV-2 and VOCs such as Omicron that employ the same receptor to infect cells and therefore has high potential to be repurposed to control, treat, or prevent coronavirus disease 2019 (COVID-19).