Repurposing of FDA approved drugs for Hereditary Angioedema – An Insilico Molecular Docking and Dynamics study

Hereditary angioedema is characterized by repeated episodes of extremely severe swelling (angioedema) of the hands, feet, limbs, face, digestive system and respiratory tract. An attack can be triggered by a minor trauma or stress, but oedema usually occurs without warning. The inflammation of the airways can lead to obstruction and difficulty breathing. It is a rare autosomal dominant disease caused by the absence or dysfunction of a C1 inhibitory protein. The current treatment for HAE includes C1 esterase inhibitors (cinryze and haegarda), Plasma kallikrein inhibitors (Lanadelumab, Berotralstat) and bradykinin B2 receptor antagonist. Patients with hereditary angioedema have benefited enormously from the boom in new drug development and approval. However, the financial consequences have made it difficult to obtain these potentially revolutionary and life-saving drugs. Thus, with the drug repurposing approach, a set of test drugs from the FDA databases was paired with the chosen target protein 7n7x. Molecular dynamics was also performed to explore the conformational space. The result showed that tropism (binding affinity of -9.1) and losartan (-8.6) showed a higher binding energy than other drugs suggesting their potential as novel therapies.