Analysis of CD147 inhibitors such as ivermectin, azithromycin with respect to their potential therapeutic use against the emerging COVID mutations

There has been reported by clinical scientists that a macrocyclic lactone such as ivermectin showed some activity against new emerging SARS CoV-2 (COVID- 19). Since a biological mechanism proposed for this anti-viral effect is not solely adequate to draw a conclusion at the phycological scale, this in silico investigation is conducted to identify potential modes of action of ivermectin against COVID-19. In this regards, vast multi target molecular simulation is considered to assess not only Ivermectin, but also other structurally similar compounds to identify a possible therapeutical solution. Ivermectin and 14 other compounds, by which the infectivity and morbidity of the SARS CoV-2 may be limited. Molecular simulations are conducted in MOE. Docking scores which represents the binding affinity between ligand and receptor are computed for all 15 agents on several docking sites for FOUR targeted proteins. These targeted proteins are all involved in infection and spreads of SARS CoV-2 virus within the human body. The first one is the spike glycoprotein of the virus, which in time, many mutations occurred in its protein sequence and consequently in its 3D structure. Therefore, the second targeted protein is the mutated spike protein. since D614G is the most common mutation among all variants, this study is focused on this specific mutation. Third protein is the CD147 human receptor which has been identified as a secondary attachment for the virus. Last considered receptor is the alpha-7 nicotinic acetylcholine receptor (α7nAChr), which is an activation site for the cholinergic anti-inflammatory pathway controlled by vagus nerve and is an indicated penetration point of neuronal tissue. Binding modes of each compound are assessed, and all the binding affinities are calculated for these multiple docking sites. Competitively high binding affinity for Ivermectin is identified and even higher binding affinities in case of other proposed compounds are reported for all four of these targeted proteins. These results suggest biological mechanisms by which ivermectin may limit the infectivity and morbidity of the both original and mutated SARS- CoV-2 virus and stimulate an α7nAChr-mediated anti-inflammatory pathway that could limit cytokine production by immune cells.