Methotrexate inhibits SARS-CoV-2 virus replication "in vitro".

Methotrexate inhibits SARS-CoV-2 virus replication "in vitro".
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DOI:
10.1002/jmv.26512
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发表时间:
2021-03
影响因子:
12.7
通讯作者:
Alberghina L
Alberghina L
中科院分区:
医学3区
文献类型:
--
作者:
Caruso A;Caccuri F;Bugatti A;Zani A;Vanoni M;Bonfanti P;Cazzaniga ME;Perno CF;Messa C;Alberghina L

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2020年初,新型呼吸综合征COVID - 19(由人畜共患的SARS - CoV - 2病毒引起)像大流行一样蔓延,从中国武汉开始,造成严重的经济萧条。尽管在治疗疾病后期并发症的药物治疗方面取得了一些进展,但由于目前没有疫苗或特定的抗病毒治疗,大流行的死亡人数是悲惨的。通过使用系统方法,我们确定了宿主编码途径,该途径为病毒RNA合成提供核糖核苷酸,作为可能的靶标。我们发现甲氨蝶呤是一种FDA批准的嘌呤生物合成抑制剂,能有效抑制病毒RNA复制、病毒蛋白合成和病毒释放。有效的抗病毒甲氨蝶呤浓度与使用相同药物的现有人类疗法相似。甲氨蝶呤应在症状出现最早的患者中最有效,以有效防止病毒复制、感染扩散和可能致命的并发症。由SARS - CoV - 2病毒引起的COVID - 19大流行是全球公共卫生威胁,造成80多万人死亡,数百万人感染,并造成严重的经济萧条。目前还没有疫苗或特定的抗病毒治疗方法。通过抑制宿主编码途径(该途径为病毒RNA合成提供核糖核苷酸),FDA批准的药物甲氨蝶呤可有效阻断SARS - CoV - 2复制。
In early 2020 the new respiratory syndrome COVID‐19 (caused by the zoonotic SARS‐CoV‐2 virus) spread like a pandemic, starting from Wuhan, China, causing severe economic depression. Despite some advances in drug treatments of medical complications in the later stages of the disease, the pandemic's death toll is tragic, as no vaccine or specific antiviral treatment is currently available. By using a systems approach, we identify the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, as a possible target. We show that methotrexate, an FDA‐approved inhibitor of purine biosynthesis, potently inhibits viral RNA replication, viral protein synthesis, and virus release. The effective antiviral methotrexate concentrations are similar to those used for established human therapies using the same drug. Methotrexate should be most effective in patients at the earliest appearance of symptoms to effectively prevent viral replication, diffusion of the infection, and possibly fatal complications. The COVID‐19 pandemic caused by the SARS‐CoV‐2 virus is a global public health threat causing over 800000 deaths, millions of infected people, and severe economic depression. No vaccine or specific antiviral treatments are currently available. By inhibiting the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, the FDA‐approved drug methotrexate efficiently blocks SARS‐CoV‐2 replication.
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