Global solvability and stability of an alarm-taxis system

This paper is concerned with the global boundedness and stability of classical solutions to an alarm-taxis system describing the burglar alarm hypothesis as an important mechanism of anti-predation behavior when species are threaten by predators. Compared to the existing prey-taxis systems, the alarm-taxis system has more complicated coupling structure and additionally requires the gradient estimate of the primary predator density to attain the global boundedness of solutions. By the sophisticated coupling energy estimates based on the Neumann semigroup smoothing properties, we establish the existence of globally bounded solutions in two dimensions with Neumann boundary conditions and furthermore prove the global stability of co-existence homogeneous steady states under certain conditions on the system parameters

Predicting the Potential Effect of E484K Mutation on the Binding of 28 Antibodies to the Spike Protein of SARS-CoV-2 by Molecular Dynamics Simulation and Free Energy Calculation

Vaccines and antibody therapeutic are needed to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has spread since 2020. Experimental studies have shown that the E484K variant may escape the neutralization of antibodies. To explore the potential impact of E484K mutation on the antibody binding affinity, we calculated the binding free energy of 28 antibodies to the wild type and K484 mutant of the spike protein of SARS-CoV-2. We found that 71% of the antibodies show lower binding affinity to the E484K mutant, indicating the highly possible immune escape risk of the mutated virus. Further analysis revealed that the other mutations, e.g. F490 and V483, are also likely to cause immune escape

Predicting spike protein NTD mutations of SARS-CoV-2 causing immune escape by molecular dynamics simulations

The emergence of coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been bringing the world to a standstill. Beyond all doubt, the most striking therapeutic target for antibody development is the spike (S) protein on the surface of virus. In contrast with an immunodominant receptor-binding domain (RBD) of the spike protein, little is known about neutralizing antibodies binding mechanisms of N-terminal domain (NTD), let alone the effect of NTD mutation on antibody binding and risk of immune evasion. Employing various computational approaches in this study, we investigated critical residues for NTD-antibody bindings and their detailed mechanism. The results showed that some residues on NTD including Y144, K147, R246 and Y248 are critically involved in the direct interaction of NTD with many monoclonal antibodies (mAbs), indicating that the viruses harboring these residue mutations may have high risk of immune evasion. Binding free energy calculations and the interaction mechanism study revealed that R246I, which is present in Beta (B.1.351) variant, may decrease or even abrogate the efficacies of many antibodies. Therefore, special attention should be paid to the mutations of the 4 residues for future antibody design and development