PT  - JOURNAL ARTICLE
AU  - Guanguan Li
AU  - Jing Sun
AU  - Yingjun Li
AU  - Yongjie Shi
AU  - Jincun Zhao
AU  - Tony Y. Zhang
AU  - Xumu Zhang
TI  - Enantiomers of Chloroquine and Hydroxychloroquine Exhibit Different Activities Against SARS-CoV-2 <em>in vitro</em>, Evidencing <em>S</em>-Hydroxychloroquine as a Potentially Superior Drug for COVID-19
AID  - 10.1101/2020.05.26.114033
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.26.114033
4099  - http://biorxiv.org/content/early/2020/07/15/2020.05.26.114033.short
4100  - http://biorxiv.org/content/early/2020/07/15/2020.05.26.114033.full
AB  - In all of the clinical trials for COVID-19 conducted thus far and among those ongoing involving chloroquine or hydroxychloroquine, the drug substance used has invariably been chloroquine (CQ) diphosphate or hydroxychloroquine (HCQ) sulfate, i.e., the phosphoric or sulfuric acid salt of a racemic mixture of R- and S-enantiomer (50/50), respectively. As a result, the clinical outcome from previous CQ or HCQ trials were, in fact, the collective manifestation of both R and S-enantiomers with inherent different pharmacodynamic and pharmacokinetic properties, and toxicity liabilities. Our data for the first time demonstrated the stereoselective difference of CQ and HCQ against live SARS-CoV-2 virus in a Biosafety Level 3 laboratory. S-chloroquine (S-CQ) and S-hydroxychloroquine (S-HCQ) were found to be 31% and 60% more active against SARS-CoV-2, as compared to R-CQ and R-HCQ, respectively. With these data and previous work on stereoselective metabolism of CQ and HCQ, we recommend that future clinical studies should employ S-HCQ as a potentially superior drug substance for the treatment of COVID-19 for improved therapeutic index.Competing Interest StatementThe authors have declared no competing interest.