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?:abstract
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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 a severe economic depression. Despite some advances in drug treatments of medical complications in later stages of the disease, the pandemic\'s death toll is tragic, since 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. This article is protected by copyright. All rights reserved.
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