scholarly journals Conserved in 186 countries the RBD fraction of SARS CoV-2 S-protein with in-silicoT500S mutation strongly blocks ACE2 rejecting the viral spike; A Molecular-docking analysis.

2021 ◽  
Author(s):  
Amrita Banerjee ◽  
Mehak Kanwar ◽  
Dipannita Santra ◽  
Smarajit Maiti
Keyword(s):  
Crystal Structure ◽  
Molecular Docking ◽  
Receptor Binding ◽  
Structural Alignment ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Docking Analysis ◽  
Global Pandemic ◽  
Complete Rejection ◽  
Molecular Docking Analysis

SARS-CoV-2 developed global-pandemic with millions of infections/deaths. Blocker/inhibitor of ACE2 and viral-spikes Receptor-Binding-Domain RBD-blockers are helpful. Here, conserved RBD (CUTs) from 186-countries were compared with WUHAN-Hu-1 wild-type by CLUSTAL-X2 and Structural-alignment using Pymol. The RBD of ACE2-bound nCOV2 crystal-structure (2.68)6VW1 was analyzed by Haddock-PatchDock. Extensive structural study/trial to introduce point/double/triple mutations in the following locations (Y489S/Y453S/T500S/T500Y)/(Y489S,Y453S/Y489S,T500S/Y489S,T500Y/Y453S,T500S/Y453S,T500Y)/ (Y489S,Y453S,T500S/Y489S,Y453S,T500Y) of CUT4 (most-effective) were tested with Swiss-Model-Expacy. Blind-docking of mutated-CUTs to ACE2 (6VW1) by Haddock-Hawkdock was performed and optimally complete-rejection of nCOV2 to ACE2 was noticed. Further, competitive-docking/binding-analyses were done by PRODIGY. Present results suggest that compared to the wild-spike, CUT4 showed extra LYS31-PHE490/GLN42-GLN498 bonding and lack of TYR41-THR500 interaction (in wild H-bond:2.639) with ACE2 RBD. Mutated-CUT4 strongly binds with the ACE2-RBD, promoting TYR41-T500S (H-bond: 2.0 and 1.8)/T500Y (H-bond:2.6) interaction and complete inhibition of ACE2 RBD-nCOV2. Mutant combinations T500S,Y489S,T500S and Y489S,Y453S,T500Y mostly blocked ACE2. Conclusively, CUT4-mutant rejects whole glycosylated-nCoV2 pre-dock/post-dock/competitive-docking conditions.

scholarly journals Conserved in 186 Countries The RBD Fraction of SARS CoV-2 S-Protein With in-Silico T500S Mutation Strongly Blocks ACE2 Rejecting The Viral Spike; A Molecular-Docking Analysis.

2021 ◽  
Author(s):  
Amrita Banerjee ◽  
Mehak Kanwar ◽  
Dipannita Santra ◽  
Smarajit Maiti
Keyword(s):  
Structural Alignment ◽  
Docking Studies ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Docking Analysis ◽  
S Protein ◽  
Global Pandemic ◽  
Complete Rejection ◽  
Molecular Docking Analysis

Abstract SARS CoV-2 developed a global pandemic with millions of infections/deaths. The role of blocker/inhibitor of ACE2 and viral-spikes Receptor-Binding-Domain RBD-blockers has been reported. In the current study, conserved RBD portions or cuts from 186 countries were screened and compared with WUHAN-Hu-1 wild-type by CLUSTAL X2 and Structural alignment analyses using Pymol. The RBD of ACE2 bound nCOV2 crystal-structure (2.68 Å) 6VYB1 was analyzed by PyMol and compared with RBD-Cut docking by Haddock and Patch Dock. Extensive structural study/trial to introduce point/double/triple mutations in the following locations (Y489S/Y453S/T500S/T500Y)/ (Y489S,Y453S/Y489S,T500S/Y489S,T500Y/Y453S,T500S/Y453S,T500Y)/ (Y489S,Y453S,T500S/ Y489S,Y453S,T500Y) of CUT4 were tested with Swiss Model Expacy. Blind docking of mutated CUTs to ACE2 (6VW1) by Haddock and Hawkdock was performed and complete rejection of nCOV2 was optimized through its re-docking trial and using pre-docked ACE2. Further, competitive-docking was performed and its binding analyses were done by PRODIGY. Present results suggest that compared to the wild-spike, CUT4 showed extra LYS31-PHE490 and GLN42-GLN498 bonding and lack of TYR41-THR500 interaction (in wild H-bond: 2.639Å) with ACE2 RBD, which can potentially but compete with the wild-spike. Whereas mutated CUT4 strongly binds with the ACE2 RBD, promoting TYR41-T500S (H-bond: 2.0Å and 1.8Å)/T500Y (H-bond: 2.6Å) interaction and complete inhibition of ACE2 RBD-nCOV2 S-protein binding. Mutant combinations T500S, Y489S,T500S and Y489S,Y453S,T500Y were found to be the most potent blocker of ACE2. It is hypothesized that Cut4 mutant is kinetically more favoured for ACE2-RBD binding and even reject whole glycosylated nCoV2 in all format of experiments; pre-dock, post-dock, and competitive-docking. Studies are necessary in this regard.

scholarly journals Molecular dynamics analysis of N-acetyl-D-glucosamine against specific SARS-CoV-2’s pathogenicity factors

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252571
Author(s):  
Ömür Baysal ◽  
Naeem Abdul Ghafoor ◽  
Ragıp Soner Silme ◽  
Alexander N. Ignatov ◽  
Volha Kniazeva
Keyword(s):  
Molecular Dynamics ◽  
Immune Response ◽  
Molecular Docking ◽  
Immune System ◽  
Receptor Binding ◽  
Binding Domain ◽  
Dynamics Analysis ◽  
Receptor Binding Domain ◽  
Docking Analysis ◽  
Molecular Docking Analysis

The causative agent of the pandemic identified as SARS-CoV-2 leads to a severe respiratory illness similar to SARS and MERS with fever, cough, and shortness of breath symptoms and severe cases that can often be fatal. In our study, we report our findings based on molecular docking analysis which could be the new effective way for controlling the SARS-CoV-2 virus and additionally, another manipulative possibilities involving the mimicking of immune system as occurred during the bacterial cell recognition system. For this purpose, we performed molecular docking using computational biology techniques on several SARS-CoV-2 proteins that are responsible for its pathogenicity against N-acetyl-D-glucosamine. A similar molecular dynamics analysis has been carried out on both SARS-CoV-2 and anti-Staphylococcus aureus neutralizing antibodies to establish the potential of N-acetyl-D-glucosamine which likely induces the immune response against the virus. The results of molecular dynamic analysis have confirmed that SARS-CoV-2 spike receptor-binding domain (PDB: 6M0J), RNA-binding domain of nucleocapsid phosphoprotein (PDB: 6WKP), refusion SARS-CoV-2 S ectodomain trimer (PDB: 6X79), and main protease 3clpro at room temperature (PDB: 7JVZ) could bind with N-acetyl-D-glucosamine that these proteins play an important role in SARS-CoV-2’s infection and evade the immune system. Moreover, our molecular docking analysis has supported a strong protein-ligand interaction of N-acetyl-D-glucosamine with these selected proteins. Furthermore, computational analysis against the D614G mutant of the virus has shown that N-acetyl-D-glucosamine affinity and its binding potential were not affected by the mutations occurring in the virus’ receptor binding domain. The analysis on the affinity of N-acetyl-D-glucosamine towards human antibodies has shown that it could potentially bind to both SARS-CoV-2 proteins and antibodies based on our predictive modelling work. Our results confirmed that N-acetyl-D-glucosamine holds the potential to inhibit several SARS-CoV-2 proteins as well as induce an immune response against the virus in the host.

scholarly journals Potential Role of Colchicine in Combating COVID-19 Cytokine Storm and Its Ability to Inhibit Protease Enzyme of SARS-CoV-2 as Conferred by Molecular Docking Analysis

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 20
Author(s):  
Noha A. Kamel ◽  
Nasser S. M. Ismail ◽  
Ibrahim S. Yahia ◽  
Khaled M. Aboshanab
Keyword(s):  
Molecular Docking ◽  
Hydrophobic Interactions ◽  
Cytokine Storm ◽  
Destructive Effect ◽  
Health Crisis ◽  
Docking Analysis ◽  
Global Pandemic ◽  
Protease Enzyme ◽  
Anti Inflammatory ◽  
Molecular Docking Analysis

Despite the advance in the management of Coronavirus disease 2019 (COVID-19), the global pandemic is still ongoing with a massive health crisis. COVID-19 manifestations may range from mild symptoms to severe life threatening ones. The hallmark of the disease severity is related to the overproduction of pro-inflammatory cytokines manifested as a cytokine storm. Based on its anti-inflammatory activity through interfering with several pro and anti-inflammatory pathways, colchicine had been proposed to reduce the cytokine storm and subsequently improve clinical outcomes. Molecular docking analysis of colchicine against RNA-dependent RNA polymerase (RdRp) and protease enzymes of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) revealed that colchicine provided a grid-based molecular docking method, C-DOCKER interaction energy 64.26 and 47.53 (Kcal/mol) with protease and RdRp, respectively. This finding indicated higher binding stability for colchicine–protease complexes than the colchicine–RdRp complex with the involvement of seven hydrogen bonds, six hydrogen acceptors with Asn142, Gly143, Ser144, and Glu166 and one hydrogen-bond donors with Cys145 of the protease enzyme. This is in addition to three hydrophobic interactions with His172, Glu166, and Arg188. A good alignment with the reference compound, Boceprevir, indicated high probability of binding to the protease enzyme of SARS-CoV-2. In conclusion, colchicine can ameliorate the destructive effect of the COVID-19 cytokine storm with a strong evidence of antiviral activity by inhibiting the protease enzyme of SARS-CoV-2.

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