Despite the success rates of the Pfizer and Moderna vaccines, COVID-19 remains a global threat. Vaccine distribution complications and slow adoption by the public create an opportunity for vaccine-resistant variants to arise. Current treatment practices, including the use of corticosteroids or intravenous immunoglobulin, are supportive, rather than therapeutic. Apart from remdesivir, an RNA-dependent RNA polymerase (RdRP)-inhibitor that inhibits coronaviruses SARS-CoV and MERS-CoV, no drugs have been FDA-approved for use as repurposable therapeutic drugs. There is an urgent need to develop new therapeutics against COVID-19.
Description
Rather than targeting viral proteins, Pitt researchers aim to exploit the natural antiviral programs that arm host cells and used a comprehensive, mechanism-unbiased, and highly integrated systems-level approach. A set of 38 priority candidate compounds targeting the host system, including repurposable and computational drugs, were identified using computational modeling. Fifteen compounds have potential antiviral actions, while 23 have possible anti-hyperinflammatory capabilities. Fourteen have been selected for in vitro assays with different cell lines. Several of these compounds inhibited SARS-CoV-2 infection in a dose-dependent manner, with two showing particular efficacy. These findings expand the repertoire of drugs and compounds that can be repurposed or developed for treating COVID-19 either independently or in combination with each other.
Applications
· Workflow for predicting drugs and compounds that interact with host cell proteins involved in viral infection and immune response to viral infection
· Development of drugs/drug combinations to treat COVID-19
Advantages
· Novel combination of computational and systems biology analyses
· Focusing on host targets enables a new series of previously unrecognized targets
· More efficient than traditional screening approaches
· Combinations of predicted drugs may synergistically increase the efficacy
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20240100018A1
