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

Med Hypotheses. 2020 Sep:142:109815. doi: 10.1016/j.mehy.2020.109815. Epub 2020 May 6.


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.

Keywords: COVID-19; Chloroquine; Hydroxychloroquine; SARS-CoV-2; Therapy; Zinc.

MeSH terms

  • Aged
  • Betacoronavirus
  • COVID-19
  • COVID-19 Drug Treatment
  • Chloroquine / administration & dosage*
  • Coronavirus Infections / drug therapy*
  • Dietary Supplements*
  • Drug Synergism
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Hydroxychloroquine / administration & dosage*
  • Length of Stay
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Male
  • Models, Theoretical
  • Pandemics
  • Patient Safety
  • Pneumonia, Viral / drug therapy*
  • SARS-CoV-2
  • Zinc / administration & dosage*
  • Zinc / pharmacology


  • Hydroxychloroquine
  • Chloroquine
  • Zinc