Urtica dioica Agglutinin: A plant protein candidate for inhibition of SARS-COV-2 receptor-binding domain for control of Covid19 Infection

• Published in: PloS one 2022-07, Vol.17 (7), p.e0268156
• Main Authors: Sabzian-Molaei, Fatemeh, Nasiri Khalili, Mohammad Ali, Sabzian-Molaei, Mohammad, Shahsavarani, Hosein, Fattah Pour, Alireza, Molaei Rad, Ahmad, Hadi, Amin
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin; Angiotensin-Converting Enzyme 2; Antiviral agents; Binding energy; Binding Sites; Biology and life sciences; Chemical properties; Chromatography; Coronaviruses; COVID-19; COVID-19 - therapy; COVID-19 Serotherapy; COVID-19 Vaccines; Crystal structure; Disease transmission; Domains; Energy; Enzyme-linked immunosorbent assay; Enzymes; Epidemics; Free energy; Genomes; Glycoproteins; Health aspects; Humans; Hydrogen bonds; Immunization, Passive; Immunoglobulin G; Immunoglobulin G - metabolism; Infections; Mathematical analysis; Medicine and health sciences; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Mutation; Peptides; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - metabolism; Pharmaceutical research; Physical Sciences; Plant Lectins; Plant proteins; Plant Proteins - metabolism; Prodigies; Protein Binding; Proteins; Receptors; Research and analysis methods; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Simulation; Spike Glycoprotein, Coronavirus - genetics; Spike protein; Toxicity; Urtica dioica; Vaccines; Viral diseases; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0268156

Despite using effective drugs and vaccines for Covid 19, due to some limitations of current strategies and the high rate of coronavirus mutation, the development of medicines with effective inhibitory activity against this infection is essential. The SARS-CoV-2 enters the cell by attaching its receptor-binding domain (RBD) of Spike to angiotensin-converting enzyme-2 (ACE2). According to previous studies, the natural peptide Urtica dioica agglutinin (UDA) exhibited an antiviral effect on SARS-CoV, but its mechanism has not precisely been elucidated. Here, we studied the interaction between UDA and RBD of Spike protein of SARS-CoV-2. So, protein-protein docking of RBD-UDA was performed using Cluspro 2.0. To further confirm the stability of the complex, the RBD-UDA docked complex with higher binding affinity was studied using Molecular Dynamic simulation (via Gromacs 2020.2), and MM-PBSA calculated the binding free energy of the system. In addition, ELISA assay was used to examine the binding of UDA with RBD protein. Results were compared to ELISA of RBD-bound samples of convalescent serum IgG (from donors who recovered from Covid 19). Finally, the toxicity of UDA is assessed by using MTT assay. The docking results show UDA binds to the RBD binding site. MD simulation illustrates the UDA-RBD complex is stable during 100 ns of simulation, and the average binding energy was calculated to be -47.505 kJ/mol. ELISA and, MTT results show that UDA binds to RBD like IgG-RBD binding and may be safe in human cells. Data presented here indicate UDA interaction with S-protein inhibits the binding sites of RBD, it can prevent the virus from attaching to ACE2 and entering the host cell.