Novel chemical compounds for use as antivirals against VEEV and other alpha viruses.
Alphaviruses like VEEV are enveloped, RNA viruses that are geographically widely distributed and are known to cause rash, arthritis, encephalitis, and death in humans. Of the more than 30 alphavirus pathogens known, about a third contributes to human disease, and currently there are no FDA approved treatments available for any of them. A renewed interest to find effective therapeutic leads for development has emerged due to the lack of effective countermeasures for these pathogens, the increased incidence of their prevalence with global climate changes, and the ease with which they can and have been weaponized as biological threats.
Use as general class antiviral Inhibitors against alphaviruses.
Probe ML336 and its analogs are being investigated as anti-VEEV lead compounds. The compounds are being assessed for efficacy against serotypes of VEEV, other alphaviruses such as WEEV and EEEV. Advanced mechanism of action studies are ongoing to confirmed specific viral protein specificity.
Novel chemotype with new scaffold; probe demonstrated VEEV-induced cytopathic effect in the low nanomolar range; favorable in vitro pharmacokinetic profile which included moderate blood-brain barrier permeability.
ML336 dramatically reduced in vitro viral titer and featured a favorable in vitro pharmacokinetic profile which included moderate blood-brain barrier permeability. These combined characteristics have delivered an advanced lead which is suitable for further drug development.
Use of ML336 as research probe for VEEV study.