Il progetto
La pandemia SARS-CoV-2 ha causato una devastante crisi sanitaria globale che ha creato e
ha rivelato molte sfide nelle nostre società attuali, inclusa la necessità di utilizzare farmaci antivirali efficaci. Un'opzione terapeutica che è stata presa in considerazione sono gli inibitori della biosintesi de novo delle pirimidine che sono antivirali per il targeting dell'ospite (HTA). Queste piccole molecole prendono di mira i fattori ospiti sfruttati da SARS-CoV-2 e sono responsabili della replicazione del virus nelle cellule infette. MEDS433, un inibitore interno della diidroorotato deidrogenasi (hDHODH), agisce come agente antivirale ad ampio spettro (BSAA), in grado di ridurre potentemente la replicazione di un grande pannello virale, incluso SARS-CoV-2.
How does it work?
By targeting hDHODH, MEDS433 is able to lead the infected cell in a condition named “pyrimidine starvation”. In such condition, the virus became unable to replicate and became prey of the immune defensive system. Such mechanism could be applied potentially to target any virus and will be effective also when the virus will start to mutate (variants) during the pandemic event.
Impact
This project will advance science through research on a unique and valuable mechanism that seems to cause molecular vulnerabilities in both RNA and DNA viruses. Strong evidence indicates how drug- like hDHODH inhibitors could be effectively used in pandemic events as BSAAs.
If the project succeeds in proving the concept of MEDS433 as an in vivo agent in SARS-CoV-2 and several respiratory viruses, a new therapeutic option will be opened and the whole pandemic scenario will be reinforced. BSAAs could be very valuable in the control of emerging and re-emerging viral diseases since the repositioning of existing safe-in-man BSAAs from a pandemic event to another is certainly faster and cheaper than the development of virus-specific drugs and vaccines.
On the news
University of Turin press release 2022 (link to Italian article)
University of Turin press release 2023 (link to Italian article)