UCLA researchers in the Department of Molecular and Medical Pharmacology have discovered a group of small molecule compounds that are active against live SARS-CoV-2 at therapeutically relevant concentrations.
BACKGROUND:
COVID-19 is a global pandemic caused by a newly discovered coronavirus, severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). SARS-CoV-2 is an enveloped positive-sense single-stranded RNA virus that enters the host cells by binding to the angiotensin converting enzyme 2 (ACE2) receptor that is expressed on both alveolar type 1 and 2 cells in the lung. To date, the disease has spread to 195 countries or territories, and the number of COVID-19 cases has surpassed 1,700,000 in the United States, with over 100,000 deaths. The major causes of morbidity and mortality from COVID-19 are acute lung injury with diffuse alveolar damage resulting in acute respiratory distress syndrome. Despite the significant threat posed by the viral infections, patients have limited treatment options. As of May 2020, the United States gave emergency use authorization (not full approval) for remdesivir, a broad-spectrum antiviral medication that was suggested to reduce the duration of recovery. However, the drug did not decrease mortality rate significantly (11.9% to 7.1%) and has been in short supply. More effective and accessible treatment options are needed to combat COVID19.
INNOVATION:
Researchers in the Department of Molecular and Medical Pharmacology have discovered a group of small molecule compounds that are active against live SARS-CoV-2 at therapeutically relevant concentrations (250nM). The compounds inhibit crucial pathways to viral replication and could be used for managing SARS-CoV-2 infections with no or low cytotoxicity of infected mammalian cells. The discovered small molecule compounds and potentially their derivatives are very promising agents against coronavirus infections and potentially other viral infections.
POTENTIAL APPLICATIONS:
•Treatment for SARS-CoV-2 infections
ADVANTAGES:
•Strong inhibition (>50%) of SARS-Cov-2 replication
•Low and therapeutically relevant inhibitory concentrations
•No or low cytotoxicity
DEVELOPMENT-TO-DATE:
The study has been validated in vitro in concentrations (250nM) relevant for therapeutic applications.