ABSTRACT
We examined the effects of mutations on domains (NID, RBM, and SD2) found at the interfaces of spike domains Omicron B.1.1529, Delta/B.1.1529, Alpha/B.1.1.7, VUM B.1.526, B.1.575.2, and B.1.1214 (formerly VOI Iota). We tested the affinity of Omicron for hACE2 and found that the wild and mutant spike proteins were using atomistic molecular dynamics simulations. According to binding free energies calculated during mutagenesis, hACE2 bound Omicron spike more strongly than SARS-CoV-2 wild strain. T95I, D614G, and E484K are three substitutions that significantly contribute to the RBD, corresponding to hACE2 binding energies and a doubling of Omicron spike proteins' electrostatic potential. Omicron appears to bind hACE2 with greater affinity, increasing its infectivity and transmissibility. The spike virus was designed to strengthen antibody immune evasion through binding while boosting receptor binding by enhancing IgG and IgM antibodies that stimulate human {beta}-cell, as opposed to the wild strain, which has more vital stimulation of both antibodies.
ABSTRACT
The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic. The FDA till yet approved a vaccine for human novel coronavirus. Here we developed a peptide-based vaccine and used high throughput screening by molecular dynamics simulation to identify T-cell and β-cell recognized epitopes to the production of specific antibodies against SARS-nCoV-2. We construct ~12 P` antigenic epitope peptides used to develop a more effective vaccine and identify specific antibody. These epitope peptides selectively best antigens presentation scores for both human pMHC- class I-II alleles to develop strong bindings affinity that were all antigens identified of SARS-nCoV-2 different proteins by each attached specific 1-7L linkers adaptor to construct a large single peripheral peptide vaccine. It is expected to be highly antigenic with a minimum allergic effect. Furthermore, considering the conservancy, this peptide vaccine promising to be highly utilized to a developed specific antibody against SARS-nCoV-2 by an initiate of T-cell and β-cell. An in-vitro study for the proposed peptide-based vaccine mostly recommended. Further clinical trials are required to check the efficacy of this vaccine.
Subject(s)
Drug HypersensitivityABSTRACT
Severe acute respiratory syndrome (SARS) is developing disease caused by novel coronavirus (COVID19). This situation has urgently prompted many pharma and R&D research companies and public research health sectors to concentrate their efforts on research for effective therapeutics. SARS-nCoV-2 as a spike (S) protein was a targeted for the development of monoclonal antibody and therapeutics for the prevention and treatment. We developed monoclonal antibody by deep mutational scanning to characterize the effects of mutations in an antibody variable fragment on its based on expression levels, specificity, stability, and affinity for antigenic specific epitope to the Spike-S-RBD. Further to make this antibody multipoint core mutations to improve contacts between specific Fv light and heavy chains to the targeted antigen of RBD. This antibody combined enhancing mutations yielding with higher binding affinity and substantially improved stability in between RBD and antibody. Overall, this antibody may well prevent into the cell interaction with RBD-hACE2 to viral entry and prevention. SARS-nCoV-Spike-S monoclonal antibodies potently inhibited SARS-nCoV-2-Spike-S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited based upon vaccination.