Drug Repositioning

In the next weeks, several drugs against malaria, HIV, or influenza will be tested for their efficiency against SARS-Cov-2.

The process of repurposing a pre-existing drug to treat another disease is commonly called “Drug Repositioning”. In 1989, Pfizer developed a drug to treat angina pectoris (chest pain due to hearth disease). Nevertheless, the huge success of this medication, called Sildenafil, was not due to its efficiency in the treatment of angina pectoris. Indeed, the drug had been found to induce erection as side effect, and for this reason it is nowadays used to treat erectile dysfunction. This was a first, surprising, and successful example of drug repositioning. Sildenafil is commonly known as “viagra”. Drug repositioning is faster and cheaper than conventional drug discovery, and it is therefore crucial to identify treatments for rare diseases. The urgency to find effective therapies for the new coronavirus induced the researchers to investigate drugs with different indication.

For interested people, the molecular mechanism of sildenafil is reported.

Erection results from smooth muscle relaxation, induced by an intracellular calcium level decrease. A key metabolite, cGMP, activates Protein Kinase G which phosphorylates proteins leading to decreased intracellular calcium concentration. cGMP accumulates intracellularly in response to nitric oxide stimulus from extra cellular sources. However, cGMP is also converted by PDE5 (a phosphodiesterase) into GMP (which in contrast can not stimulate PKG). Sildenafil acts as a competitive inhibitor of this enzyme because of its structural similarity, thereby preventing the conversion of cGMP into GMP, rendering more cGMP available for the downstream pathway for smooth muscle relaxation. This molecular process allows to stimulate smooth muscle relaxation. #immunology#pharmacology#covid19#coronavirus#drugs#drugrepositioning#therapies#medicine#health#science#pharmacyschool#viagra#sildenafil