Abstract
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.
【저자키워드】 COVID-19, SARS-CoV-2, Zinc, therapy, Chloroquine, Hydroxychloroquine, 【초록키워드】 Treatment, clinical trials, cardiovascular disease, antiviral effects, diabetes, virus, antimalarial, RNA-dependent RNA polymerase, morbidity and mortality, HCQ, monotherapy, SARS-CoV-2 replication, metabolite, COVID-19 patients, lysosome, clinical study, Combination, Coronavirus replication, Elderly patient, host cells, deficiency, chronic pulmonary disease, candidate, zinc supplementation, effective, limit, Extracellular, tested, inhibit, occur, reducing, interfere, intracellular vesicle, 【제목키워드】 Clinical efficacy, chloroquine/hydroxychloroquine, zinc supplementation, ENhance,