A synthetic stigmastane displays antiadenoviral activity and reduces the inflammatory response to viral infection

Abstract

Although human adenovirus (ADV) infections are mild and self-limited in immunocompetent individuals, they can be severe and life-threatening in immunocompromised patients. Despite their significant clinical impact, there are not currently approved antiviral therapies for ADV infections. On the other hand, in some cases, the immune response induced by ADV infection can cause tissue damage. Even more, in the case of adenovirus vectors used in gene therapy, host immunity generally antagonize viral efficacy. Therefore, the need for searching an effective and safe therapy is increasing. In this work, we describe the antiadenoviral activity of the synthetic stigmastane (22S,23S)- 22,23-dihydroxystigmast-4-en-3-one (Compound 1) with already reported antiviral and antiinflammatory activities against other viruses of clinical importance. Compound 1 displayed no virucidal activity and did not affect ADV entry to the cells. The compound inhibited viral replication and it also reduced cytokine secretion in epithelial and inflammatory infected cells. Thus, Compound 1 would be a promissory drug potentially useful against adenoviral infections as well as an adjuvant of adenoviral vectors in gene therapy.