Antimalarial drugs inhibit the replication of SARS-CoV-2: An in vitro evaluation
Antimalarial drugs inhibit the replication of SARS-CoV-2: An in vitro evaluation
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DOI：
10.1016/j.tmaid.2020.101873
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发表时间：
2020-09-01
影响因子：
12
通讯作者：
Pradines, Bruno
中科院分区：
文献类型：
--
作者：
Gendrot, Mathieu;Andreani, Julien;Pradines, Bruno
2019年12月，引起冠状病毒病的新型严重急性呼吸综合征冠状病毒(新冠肺炎)在武汉出现，中国。非洲国家新冠肺炎病例和死亡人数增长较慢。可能解释非洲，尤其是疟疾流行地区后来出现这种情况的假设之一是使用抗疟疾药物。我们研究了几种抗疟疾药物的体外抗SARS-CoV-2活性。氯喹(EC50=2.1亩M和EC90=3.8亩M)、羟基氯喹(EC50=1.5亩M和EC90=3.0亩M)、铁喹(EC50=1.5亩M和EC90=2.4亩M)、脱乙基氨基二喹(EC50=0.52亩M和EC90=1.9亩M)、甲氟喹(EC50=1.8亩M和EC90=8.1亩M)，咯萘啶(EC50=0.72 mU M和EC90=0.75 mU M)和奎宁(EC50=10.7 mU M和EC90=38.8 mU M)具有体外抗病毒活性，IC50和IC90与治疗疟疾常用剂量的口服给药剂量相容。C-肺/EC90比值为5~59。鲁米芬、哌喹和双氢青蒿素的IC50和IC90太高，达不到预期的血药浓度(比值C-max/EC90和0.05)。根据我们的结果，我们预计，通常使用青蒿琥酯-阿莫地喹或青蒿琥酯-甲氟喹的国家报告的病例和死亡人数少于使用蒿甲醚-鲁米芬净或双氢青蒿素-哌喹的国家。现在可能有必要逐个国家比较新冠肺炎的抗疟疾使用情况和动态，以证实这一假设。
In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. African countries see slower dynamic of COVID-19 cases and deaths. One of the assumptions that may explain this later emergence in Africa, and more particularly in malaria endemic areas, would be the use of antimalarial drugs. We investigated the in vitro antiviral activity against SARS-CoV-2 of several antimalarial drugs. Chloroquine (EC50 = 2.1 mu M and EC90 = 3.8 mu M), hydroxychloroquine (EC50 = 1.5 mu M and EC90 = 3.0 mu M), ferroquine (EC50 = 1.5 mu M and EC90 = 2.4 mu M), desethylamodiaquine (EC50 = 0.52 mu M and EC90 = 1.9 mu M), mefloquine (EC50 = 1.8 mu M and EC90 = 8.1 mu M), pyronaridine (EC50 = 0.72 mu M and EC90 = 0.75 mu M) and quinine (EC50 = 10.7 mu M and EC90 = 38.8 mu M) showed in vitro antiviral effective activity with IC50 and IC90 compatible with drug oral uptake at doses commonly administered in malaria treatment. The ratio C-lung/EC90 ranged from 5 to 59. Lumefantrine, piperaquine and dihydroartemisinin had IC50 and IC90 too high to be compatible with expected plasma concentrations (ratio C-max/EC90 < 0.05). Based on our results, we would expect that countries which commonly use artesunate-amodiaquine or artesunate-mefloquine report fewer cases and deaths than those using artemether-lumefantrine or dihydroartemisinin-piperaquine. It could be necessary now to compare the antimalarial use and the dynamics of COVID-19 country by country to confirm this hypothesis.