| چکیده انگلیسی مقاله |
Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) is an infectious cause with exceptional character of is swift outbreak which lead to epidemic far away from where it was first observed in Wuhan, China [1]. SARS-COV-2 neutralizing antibodies primarily target trimeric spike glycoproteins on viral surface and mediate entry into host cells [2,3]. This spike protein has two functional subunits that mediate cell attachment and fusion of viral and cellular membrane [4]. The spike proteins of SARS-CoV-2 commonly bind to human angiotensin coverting enzyme 2 (ACE2) protein as a host receptor [5]. Nanobody refers to a group of the single-domain antibody (sdAb) that were first engineered from heavy-chain antibodies naturally found in camelids and overcome many application problems of monoclonal antibodies in molecular imaging, diagnostic kits and therapeutic medicines [6-7]. Blocking ability of spike receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) theoretically was checked with some nanobodies. Firstly, 21 of Lama glama VHH that neutralized the viral glycoprotein of Severe acute respiratory syndrome coronavirus 1 (SARS-COV-1), Middle East respiratory syndrome (MERS), Human immunodeficiency viruses 1 (HIV-1) or respiratory syncytial virus (RSV) was selected from structural antibody database (SAbDab) [8]. Then, ACE2 and each nanobody complexes with RBD were verified using CoDockPP Server [9] which provide a multistage protein-protein molecular docking based on shape complementarity that knowledge-based scoring function and site constraint. In the following, best conformation and binding energy of ACE2-RBD and VHH-RBD complexes were obtained by COVID-19 Docking Server [10]. The binding energy of RBD-ACE2 complex was recognized when RBD (6LZG (B)) and ACE2 (6LZG (A)) respectively was defined as target and ligand proteins and vice versa. It was seen, JM4, F-VHH-L66, VHH-72, and VHH A12 respectively was proposed for neutralization of spike RBD with an estimated binding energy greater than -792.4 (kcal/mol) for ACE2. The PDB ID (VHH chain name) of proposed are 4LAJ (H), 6WAQ (A), 5TOK (E), 5TOK (D), 4LAJ (L), 6WAQ (C), 4LAJ (M) and 3RJQ (B). It should be noted that the different crystallography structures of F-VHH-L66 (5TOK (E)) and (5TOK (D)) could be due to various experimental contact region of spike glycoprotein that experimentally was involved. The estimated binding energy for these VHH respectively -341.45, -333.08, -332.49, -321.6, -320.98, -320.39, -317.03 and -312.29 (kcal/mol). This study provide a molecular basis for the blocking of RBD of SARS-COV-2 with 13 proposed natural nanobody that suggest for therapeutics aim of the SARS-COV-2. |
