Testing the activity of biguanide derivatives and some novel molecules against SARS-CoV-2, in silico study

SARS-CoV-2 proteins are the main factors responsible for the replication process of the virus, including main protease (MPro), papain like protease (PLPro) and RNA dependent RNA polymerase (RdRp). Through our study, we aim to inhibit the roles of these proteins, by applying molecular docking to investigate the effectiveness of biguanide derivatives and some phytochemicals extracted from Cameroonian plants against these targets, then a molecular dynamic simulation method was applied to investigate the stability of the complexes of best docking results. Also, in silico we modified biguanide derivatives to get better results, and as the last step, we applied Absorption, Distribution, Metabolism, Excretion and Toxicity test (ADMET) to these modified compounds which showed good docking results. As a result of our study, phenformin played an inhibition role against RdRp protein, proguanil was recommended for use against PLPro, and Pycnanthuquinone B had a good result against Mpro, at the same time, 10 of our modified compounds gave promise results against these targets, so other drug development steps could be applied to investigate this activity.