This study describes the discovery of a new class of sartans bearing symmetric anionic tetrazoles, termed “bisartans”, and their potential benefits in SARS-CoV-2 treatment. Specifically, these molecules bind more strongly to the SARS-CoV-2 RBD/ACE2 complex compared to other common sartans. Bisartans also block the critical amino acid arginine in the furin cleavage site of the virus, which catalyzes the cleavage of the spike protein and is required for SARS-CoV-2 entry into host cells. Moreover, they exhibit stronger binding to the 3CLpro main protease of SARS-CoV-2, a critical enzyme for viral replication. Since bisartans act concurrently at three separate targets, essential for viral infection and replication (i.e., ACE2, furin, 3CLpro), they are promising chemistries for clinical trials.
Pubmed
Discovery of a new generation of angiotensin receptor blocking drugs: Receptor mechanisms and in silico binding to enzymes relevant to SARS-CoV-2. Ridgway H, Moore GJ, Mavromoustakos T, Tsiodras S, Ligielli I, Kelaidonis K, Chasapis CT, Gadanec LK, Zulli A, Apostolopoulos V, Petty R, Karakasiliotis I, Gorgoulis VG, Matsoukas JM.Comput Struct Biotechnol J. 2022;20:2091-2111. doi: 10.1016/j.csbj.2022.04.010. Epub 2022 Apr 9.