G6PD and chloroquine: selecting the treatment against SARS-CoV-2?

In light of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) pandemic and the possible widespread use of chloroquine (a member of the drug class 4-aminoquinoline primarily used to prevent and treat malaria and amebiasis) and its derivatives (e.g. hydroxychloroquine, a metabolite of chloroquine),(1) a safety issue is addressed, concerning the selection of patients suitable to receive it. HCov-229E is one of the four flu-causing coronaviruses which share great sequence similitude, while many symptoms of patients infected with COVID-19 resemble those of patients infected with these known flu-causing coronaviruses.(2) A previous study reported that human lung epithelial A549 cells treated with glucose 6-phosphate dehydrogenase (G6PD) interfering RNA (RNAi) to lower G6PD activity displayed augmented (12-fold) viral production in comparison to normal counterparts when infected with coronavirus HCov-229E. Moreover, viral replication in these G6PD-deficient cells was found to be 3-fold higher than normal cells, following a 10-h incubation, as estimated by quantitative polymerase chain reaction (qPCR).(3) G6PD deficiency remains the most common human enzymatic disorder of red blood cells worldwide.