Project Overview
The SARS-CoV-2 pandemic has caused a devastating global health crisis, which created and
revealed many challenges in our current societies, including the need to deploy effective antiviral drugs. One therapeutic option that has been considered is de novo pyrimidines biosynthesis inhibitors which are Host Targeting Antivirals (HTA). These small molecules target host factors exploited by SARS-CoV-2 and are responsible for virus replication in infected cells. MEDS433, an in house dihydroorotate dehydrogenase (hDHODH) inhibitor, acts as Broad Spectrum Antiviral Agent (BSAA), able to potently reduce the replication of a large virus panel, including 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)