Does zinc supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win today's battle against COVID-19?

• Published in: Medical hypotheses Vol. 142; p. 109815
• Main Authors: Derwand, R., Scholz, M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.09.2020; The Authors. Published by Elsevier Ltd
• Subjects: Aged; Betacoronavirus; Chloroquine; Chloroquine - administration & dosage; Coronavirus Infections - drug therapy; COVID-19; Dietary Supplements; Drug Synergism; Female; Humans; Hydrogen-Ion Concentration; Hydroxychloroquine; Hydroxychloroquine - administration & dosage; Length of Stay; Lysosomes - drug effects; Lysosomes - metabolism; Male; Models, Theoretical; Pandemics; Patient Safety; Pneumonia, Viral - drug therapy; SARS-CoV-2; Therapy; Zinc; Zinc - administration & dosage; Zinc - pharmacology; COVID-19; Therapy; SARS-CoV-2; Hydroxychloroquine; Chloroquine; Zinc
• ISSN: 0306-9877; 1532-2777; 1532-2777
• DOI: 10.1016/j.mehy.2020.109815

Currently, drug repurposing is an alternative to novel drug development for the treatment of COVID-19 patients. The antimalarial drug chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are currently being tested in several clinical studies as potential candidates to limit SARS-CoV-2-mediated morbidity and mortality. CQ and HCQ (CQ/HCQ) inhibit pH-dependent steps of SARS-CoV-2 replication by increasing pH in intracellular vesicles and interfere with virus particle delivery into host cells. Besides direct antiviral effects, CQ/HCQ specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication. As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials.