Methotrexate inhibits SARS‐CoV‐2 virus replication “in vitro”
Arnaldo Caruso, Francesca Caccuri, Antonella Bugatti, Alberto Zani, Marco Vanoni, Paolo Bonfanti, Marina Elena Cazzaniga, Carlo Federico Perno, Cristina Messa, Lilia Alberghina
Abstract
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.