Sunshine Biopharma announces publication of coronavirus research results

Sunshine Biopharma announced the publication of new research results in the Journal of Medicinal Chemistry. The published data demonstrate a novel PLpro inhibitor with submicromolar potency and in vivo efficacy in a mouse model of SARS-CoV-2 infection. This peer-reviewed study marks an important milestone for Sunshine Biopharma in its effort to develop an effective treatment for SARS-CoV-2 infection. There are still unmet medical needs to combat SARS-CoV-2 infection. SARS-CoV-2 undergoes mutation at a rapid rate, which leads to the continuous emergence of variants of concern posing a significant threat to public health. In addition, certain populations, such as immunocompromised patients who are susceptible to severe and prolonged infections, may not respond well to current therapies or vaccines. For high-risk patients, blocking early infection at home may prevent disease rapid progression and reduce hospitalization. PLpro is a compelling therapeutic target for developing antiviral compounds against SARS-CoV-2. It is a virus encoded protease essential for viral replication and is responsible for suppression of the human immune system following infection by the virus. The active site of an enzyme is almost always the primary target for drug design. PLpro eluded scientist for many years due to its featureless active site. To address the challenge of PLpro’s indistinct active site, we designed and synthesized a noncovalent inhibitor library targeting a vulnerability in PLpro remote from the active site incorporating the “BL2-groove”, a key feature discovered by project co-lead, Prof. Rui Xiong of the University of Arizona. One of the 50 compounds, XR8-23, had an enzyme inhibition activity of 0.39 microM and exhibited a broad spectrum of antiviral activity towards at least 4 strains of VOC including WA1/2020, Gamma, Delta, and Omicron. It had over 10-fold of selective accumulation in the lungs than in plasma and exhibited in vivo activity in a mouse-adapted SARS-CoV-2 infection at 10 mg/kg by repeated IV injections.