Favipiravir's Surprising Role as a PDE5 Inhibitor a New Therapeutic Frontier

A global increase in ED and decreased sexual activity during the COVID pandemic is reported. Favipiravir, a well-known antiviral agent used as anti-covid agent in various countries during the covid pandemic was examined for any role in ED and the results are reported in this article. Potent anti- human PDE5 activity in-vitro and such an activity was established through molecular docking of favipiravir with human PDE5 using Autodock Vina and assessment of the effect of favipiravir on the PDE5 activity was done using estimation of formation of GMP from cGMP and analysis using HPLC based method. Favipiravir, an effective antiviral agent was found to exhibit potent anti-PDE5 activity through docking studies. The identification of Phe820 as a key residue for ligand stabilization with all well-known ED drugs like Tadalafil, Sildenafil and Verdanafil and favipirvir, supports its role in the specificity of PDE5A for cGMP and its inhibition by these molecules. This suggest the possible mode of inhibition of human PDE5A by the antiviral favipiravir and is possibly the first report of an antiviral compound having potential of inhibiting PDE5, the key target enzyme associated with ED, and paves the way for incorporating antiviral compounds with the potential to address viral-associated erectile dysfunction. Favipiravir appears to be relatively safe for male reproductive health at therapeutic doses, hence its potential for addressing ED can be explored.