De novo design of a peptide-based LCB۱ inhibitor containing iron ion with theability to fight SARS-CoV-۲ infection

Background and Objective: Lactoferrin (LF) is a nutrient naturally found in mammalian milk. It is aglycoprotein of about ۷۸ kDa and possesses two Fe۳+ ions with high affinity. The naturally occurringiron chelator Lf exerts immunomodulatory as well as anti-inflammatory effects. Furthermore, there isevidence that LF can bind to some of the receptors used by coronaviruses (e.g., the angiotensinconvertingenzyme ۲ (ACE۲) and consequently block their entry. On the other hand, since the backbone,alignment of beta strands around the central axis in beta barrels and alpha helices were attracted to thestructural biologists. With regard to the first and last strand, there is a hydrogen bond in the β-barrels ofindividual beta sheets that twist to form a closed structure. Anti-parallel β-barrels are great scaffolds forligand binding since the barrel can be provided a hydrophobic core to stability in the base and the abovebarrel can be made low cavity to ligand binding frequently flanked by loops which can chip in furtherbinding affinity and selectivity. So promises high stability of these molecules with therapeutic purposes,and unlike antibodies do not lose their properties at high temperatures, therefore it is a strong preventivetreatment for diseases such as influenza and corona. Therefore, peptides have been designed de-novo(LCB۱) for the RBD sequence that can inhibit corona in the Pico molar range. Considering all the abovementionedfacts, this study aimed to investigate the possible benefits of adding iron LF to the de-novo(LCB۱) peptide to increase host immunity in coronavirus infections or not.Methods: For this purpose, the de-novo (LCB۱) peptide was modeled and tested by Itasser server,Modeler, Pymol, and Spdbv software, while LF (in two different isoforms, LF-α with and LF-β withoutiron ions) was positioned in the de-novo (LCB۱) loop individually. In addition, molecular docking wasperformed using the Haddock server and the rate of peptide binding was examined with and without ironpresence.Results: The results indicated that the presence of iron ions in the de-novo (LCB۱) peptide had nobeneficial effect on the prevention of coronavirus disease infection although we expected to have moreantiviral activity by Metal-based drugs. The obtained results also specified that the binding energy of thetwo mentioned molecules was more robust when there were no iron ions.Conclusion: we hope that the designed peptide (Lactoferrin plus LCB۱) may contribute usefully to theprevention and treatment of coronavirus infection.

کلیدواژه ها:

De novo (LCB۱) ، Lactoferrin ، Metal-based drugs ، Spike protein