In view of the emerging COVID‑19 pandemic caused by SARS‑CoV‑2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID‑19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS‑CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin‑converting enzyme 2 (ACE2), known to be the receptor for SARS‑CoV‑2.
Improved antiviral immunity by zinc may also occur through up‑regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti‑inflammatory activity by inhibiting NF‑κB signaling and modulation of regulatory T‑cell functions that may limit the cytokine storm in COVID‑19.
Improved Zn status may also reduce the risk of bacterial co‑infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID‑19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID‑19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator‑induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.
Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review)
ANATOLY V. SKALNY1,2*, LOTHAR RINK3*, OLGA P. AJSUVAKOVA2,4, MICHAEL ASCHNER1,5, VIKTOR A. GRITSENKO6, SVETLANA I. ALEKSEENKO7,8, ANDREY A. SVISTUNOV1, DEMETRIOS PETRAKIS9, DEMETRIOS A. SPANDIDOS10, JAN AASETH1,11, ARISTIDIS TSATSAKIS1,9 and ALEXEY A. TINKOV1,2,6*
1I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow; 2Yaroslavl State University, 150003 Yaroslavl, Russia; 3Institute of Immunology, Medical Faculty, RWTH Aachen University, D-52062 Aachen, Germany; 4Federal Research Centre of Biological Systems and Agro‑technologies of the Russian Academy of Sciences, 460000 Orenburg, Russia; 5Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; 6Institute of Cellular and Intracellular Symbiosis, Russian Academy of Sciences, 460000 Orenburg; 7I.I. Mechnikov North‑Western State Medical University, 191015 St. Petersburg; 8K.A. Rauhfus Children’s City Multidisciplinary Clinical Center for High Medical Technologies, 191000 St. Petersburg, Russia; 9Center of Toxicology Science and Research, 10Laboratory of Clinical Virology, Medical School, University of Crete, 71409 Heraklion, Greece; 11Research Department, Innlandet Hospital Trust, 3159894 Brumunddal, Norway
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, DOI: 10.3892/ijmm.2020.4575