Sunshine Biopharma, University of Arizona develop series of protease inhibitors

Sunshine Biopharma (SBFM) has developed a new series of orally active, non-covalent protease inhibitors with dose-dependent antiviral activity in mice infected with SARS Coronavirus. This work was carried out at the University of Arizona as part of an ongoing collaboration between the Company and the University. SARS-CoV-2 is the etiologic agent of COVID-19 and one of three types of Coronavirus that cause Severe Acute Respiratory Syndrome. The other two are SARS-CoV and MERS-CoV. For persons exposed to SARS-CoV-2, blocking early infection at home may prevent rapid disease progression and reduce hospitalization. PLpro is an alternative therapeutic target for developing antiviral compounds against proteolytic processing activity of SARS-CoV-2. PLpro is a virus encoded protease essential for viral replication and is responsible for suppression of the human immune system following infection, leading to a more severe disease outcome.The company said, “Previously we had reported that the Company’s lead compound had favorable pharmacokinetics properties, including oral availability, in mice, rats and dogs. It was found to be efficacious in a K18-human-ACE2 transgenic mouse model to block SARS-Cov-2 infection in a dose-dependent manner. In August 2024, Sunshine Biopharma published initial research results on its PLpro inhibitors library in the Journal of Medicinal Chemistry. Currently, we report that we have successfully designed and synthesized a second novel chemical series of PLpro inhibitors, which are potent against the PLpro enzyme and exhibited dose-dependent efficacy in cellular models of SARS-CoV-2 infection. These new molecules are orally active in mice and have displayed favorable pharmacokinetics profiles. Work is currently in progress to analyze their dose-dependent efficacy in mice infected with SARS-CoV-2.”