UCLA researchers from the Department of Molecular and Medical Pharmacology have identified potent drug candidates inhibiting monkeypox virus, which may be used as therapies to prevent or treat viral infections.
BACKGROUND: Monkeypox (mpox) is a viral infection related to smallpox that manifests as a rash, lesions, swollen lymph nodes, and flu-like symptoms. While symptoms are typically mild, mpox can be severe in children, as well as those who are immunosuppressed or pregnant.
The first human case of mpox was diagnosed in 1970 in Central and West Africa, where the disease is endemic. Since then, the number of cases in European countries and the United States has risen steeply. In 2022, a global outbreak resulted in 32,000 infections and 58 deaths in the United States. In August 2024, the World Health Organization declared a mpox outbreak a Public Health Emergency of International Concern. There are currently no treatments for mpox other than supportive care and symptom relief. Thus, it is prudent that drugs are developed to prevent and treat mpox infection.
INNOVATION: UCLA researchers have identified 19 antiviral compounds targeting monkeypox. They screened a kinase inhibitor library of 2750 small molecules to identify compounds that inhibited monkeypox virus (MPXV) infection in human cells. From this screen, they further identified signaling pathways that may be important for MPXV infection and replication. Researchers then conducted a secondary screen using selected inhibitors to determine which inhibitors were most potent. From this, they confirmed 19 potent drug candidates that effectively inhibit MPXV by targeting different kinases. Researchers selected the top drug hits and tested them in a mouse model of MPXV infection, where two of drugs demonstrated potent antiviral activity in vivo. These findings highlight promising new therapeutic avenues for antiviral therapy against MPXV.
POTENTIAL APPLICATIONS:
- Treating and preventing monkeypox infection
- Identifying mechanisms of infection (e.g. with identified signaling pathways and kinases) to develop new drugs or treatments
ADVANTAGES:
- Top compounds have been proven to be potent and effective mpox inhibitors in vivo
- Other inhibitors of the kinases/pathways targeted by these compounds are already in clinical trials already for other diseases
- Novel kinase targets identified for monkeypox virus infection
DEVELOPMENT-TO-DATE: UCLA researchers have identified 19 potent inhibitors of monkeypox in an in vitro high throughput screen. The most promising compounds identified in vitro have been tested and validated in mice.
Keywords: Mpox, vaccine, kinase inhibitor, high throughput screen, small molecule inhibitor, viral infection