UCLA researchers in the Department of Biological Chemistry have implicated a novel marker in SARS-CoV-2 infection, identifying a novel drug target for therapeutics treating COVID-19.
BACKGROUND
Severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2, is the virus responsible for the 2019 global pandemic (COVID-19): which caused hundreds of millions of infections and millions of eventual deaths worldwide. While effective vaccines against SARS-CoV-2 have now been developed, therapeutics to treat disease onset are only somewhat efficacious, and can require regiments to begin early in the disease onset. While vaccination rates continue to climb in the United States and other developed countries, developing countries continue to lag in their vaccination efforts: driving forward viral variants. Breakthrough infections, where the SARS-CoV-2 virus infects vaccinated individuals, are becoming increasingly common with the prevalence of new strains of the virus appearing. Unfortunately, the drug Remdesivir has relatively low effectiveness at treating SARS-CoV-2 infections and is extremely expensive for patients who typically only use it as a last resort. As a result of this poor current standard of care, it is paramount that next-generation therapeutics for COVID-19 are available both to unvaccinated individuals and those affected with breakthrough infections of SARS-CoV-2.
INNOVATION
UCLA researchers in the Department of Biological Chemistry have implicated a novel druggable target in SARS-CoV-2 infection, potentially allowing for the development of therapeutic inhibitor molecules to treat COVID-19. Cell culture studies mimicking the environment and cell types found in the human lungs have identified that a protein responsible for modulating cellular metabolism (mTORC1) is upregulated in SARS-CoV-2 infection. Furthermore, the research group identified increased mTORC1 activity after infection in cell cultures expanded from stem cells taken from patients with healthy lungs and those with lung fibrosis. Importantly, clinically-used inhibitors of mTORC1 were found to reduce SARS-CoV-2 virus replication in cultured lung cells. This discovery has revealed a novel biomarker identified during SARS-CoV-2 infection and could allow novel treatments of COVID-19.
POTENTIAL APPLICATIONS:
• Treatment of COVID-19 infections
• Advance understanding of the mechanism of SARS-CoV-2.
ADVANTAGES:
• Potential to be a cost-effective targeting strategy.
• Novel drug target adds to the relatively small repertoire of druggable molecules to treat COVID-19
DEVELOPMENT-TO-DATE: UCLA Researchers have demonstrated increased activity of mTORC1 in cells replicating healthy and fibrotic lung tissue after a challenge with SARS-CoV-2.
RELATED PAPERS:
Mullen, P. J. et al. SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition. Nat Commun 12, 1876 (2021).