A possible application of hinokitiol as a natural zinc ionophore and anti-infective agent for the prevention and treatment of COVID-19 and viral infections

Abstract

Zinc and the combination with zinc ionophore have been reported in basic research and several clinical investigations as a potentially viable and economical preventive and therapeutic options for COVID-19 treatment. Zinc is a vital microelement that actively supports respiratory epithelium barrier integrity, innate and adaptive immune functions, and inflammatory regulations. Moreover, zinc may also prevent viral entry, suppress viral replication, and mitigate the damages due to oxidative stress and hyperinflammatory reaction in patients with respiratory infections. Hinokitiol (β-thujaplicin) is a natural monoterpenoid and is considered as a safe zinc ionophore to help zinc transport into cells. It has been widely used in skin and oral care, and therapeutic products for its potent antiviral, antimicrobial, antifungal, anti-inflammatory, and anticancer applications. The ongoing COVID-19 pandemic and the significant morbidity and mortality exist in the high-risk group of patients associated with other respiratory infections such as influenza, respiratory syncytial virus, and dengue fever. There is an urgent need for the development of inexpensive, safe, and effective therapeutics to prevent and treat these viral infections. Considering that hydroxychloroquine (HCQ), the most studied zinc ionophore drug for COVID-19, is linked to potentially serious side effects, we propose the implementation of hinokitiol as a zinc ionophore and anti-infective agent for the prevention and treatment of COVID-19 and other viral infections.

The effects of some essential and toxic metals/metalloids in COVID-19: A review

“…In this same line, Kumar et al (2020) also hypothesized that zinc administration might be beneficial for the prophylaxis and treatment of COVID-19. On the other hand, Hoang and Han (2020) suggested the possible application of hinokitiol (β-thujaplicin), which is a natural monoterpenoid considered as a safe zinc ionophore for the prevention and treatment of COVID-19, as well as other viral infections. Hinokitiol would help zinc to be transported into cells.…”

Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity

“…The immunomodulatory and antiviral activities of zinc have made this mineral and its ionophores candidates against COVID-19 ( 31 , 32 ). Zinc is essential for the integrity of the immune system ( 33 ), with an important role in the maintenance, development and activation of cells during innate and adaptive immune responses.…”

Natural Bioactive Molecules: An Alternative Approach to the Treatment and Control of COVID-19

“…Zinc’s immunomodulatory and antiviral properties have made it and its ionophores potential COVID-19 targets [ 209 , 210 ]. Zinc is crucial for immune system integrity, and it plays a key role in cell maintenance, development, and activation throughout innate and adaptive immunological responses.…”