Investigation of the mutated antimicrobial peptides to inhibit ACE2, TMPRSS2 and GRP78 receptors of SARS-CoV-2 and angiotensin II type 1 receptor (AT1R) as well as controlling COVID-19 disease

Abstract

SARS-CoV-2 is a global problem nowadays. Based on studies, some human receptors are involved in binding to SARS-CoV-2. Thus, the inhibition of these receptors can be effective in the treatment of Covid-19. Because of the proven benefits of antimicrobial peptides (AMPs) and the side effects of chemical drugs, they can be known as an alternative to recent medicines. RCSB PDB to obtain PDB id, StraPep and PhytAMP to acquire Bio-AMPs information and 3-D structure, and AlgPred, Toxinpred, TargetAntiAngio, IL-4pred, IL-6pred, ACPred and Hemopred databases were used to find the best score peptide features. HADDOCK 2.2 was used for molecular docking analysis, and UCSF Chimera software version 1.15, SWISS-MODEL and BIOVIA Discovery Studio Visualizer4.5 were used for mutation and structure modeling. Furthermore, MD simulation results were achieved from GROMACS 4.6.5. Based on the obtained results, the Moricin peptide was found to have the best affinity for ACE2. Moreover, Bacteriocin leucocin-A had the highest affinity for GRP78, Cathelicidin-6 had the best affinity for AT1R, and Bacteriocin PlnK had the best binding affinity for TMPRSS2. Additionally, Bacteriocin glycocin F, Bacteriocin lactococcin-G subunit beta and Cathelicidin-6 peptides were the most common compounds among the four receptors. However, these peptides also have some side effects. Consequently, the mutation eliminated the side effects, and MD simulation results indicated that the mutation proved the result of the docking analysis. The effect of AMPs on ACE2, GRP78, TMPRSS2 and AT1R receptors can be a novel treatment for Covid-19. Communicated by Ramaswamy H. Sarma