Could 4-Phenylbutyric (4-PBA) Treat Severe Inflammatory Responses to COVID-19? Spanish Investigators Think So

Could 4-Phenylbutyric (4-PBA) Treat Severe Inflammatory Responses to COVID-19 Spanish Investigators Think So

A research team led from the University of Malaga (UMA) and the Andalusian Center for Nanomedicine and Biotechnology (BIONAND) identified 4-phenylbutyric acid or 4-PBA as a potential candidate to target what are identified as severe consequences associated with COVID-19, including inflammatory and immune challenges. By employing animal models in preclinical research, the research team assessed how 4-PBA controls the inflammatory reactions generated in severe cases of COVID-19.

With results recently published in the journal Cytokine and Growth Factors Review, the Spanish and California-based researchers center their attention on the need to control the cytokine storm, that dangerous event or series of events when COVID-19 triggers uncontrolled and disproportionate release of cytokines, that is, those molecules charged with organizing the body’s own defense.

The Drug

Around since the 1980s for the treatment of urea cycle disorders, 4-PBA directly can inhibit or reduce the impact of folded or aggregated proteins and critically has been known to directly reduce the inflammatory impact of a number of diseases and disorders, from cardiovascular and pulmonary disease to a number of other conditions, such as liver failure.

An anti-stress treatment, the study team has the repurposing of 4-PBA in their strategic imperative. Approved by regulators already, 4-PBA could possibly modulate stress and apply to other conditions as well.


Led by Dr. Ivan Duran and Dr. Fabiana Csukasi, researchers will continue to investigate how and why 4-PBA controls inflammatory reactions associated with SARS-CoV-2. Dr. Ivan Duran reports that, “Our preliminary results conducted on animal models have demonstrated that 4-PBA fully curbs mortality caused by respiratory failure derived from cellular stress.”

The team has reported that their initial research reveals that the endoplasmic reticulum resident protein called “BiP” (Binding Immunoglobulin Protein), a stress blood marker, also indicates cellular stress situations.


This preliminary research was funded by the COVID-19 Fund of the Government of Andalusia, including an initial endowment of €90,000 with the possibility of renewal in three years.

Lead Research/Investigators

Ivan Duran, Orthopaedic Surgery, UCLA

Fabiana Csukasi, Department of Orthopaedic Surgery, UCLA

Gustavo Rico, Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Malaga, IBIMA, Spain

Jose Becerra, Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Malaga, IBIMA, Spain