Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
The operation mode of microgrids influences the dispatching management of distribution system in the power market. The study uses game theory to study dispatching strategies between multi-microgrid in the distribution system. For this purpose, a two-level game model of multi-microgrid dispatching in the electricity market is proposed. Firstly, the upper level of the model researches the answer of a basic question for a multi-microgrid distribution system that what the boundary line between noncooperation mode and coalition mode is. Secondly, by the lower level of the model, multi-microgrid decides the operation mode ultimately when it is uncertain in the upper level of model. The upper level is a non-cooperative price game between multimicrogrid and distribution system while the lower level is a cooperative trading loss cost game. In order to optimise multimicrogrid dispatching, an algorithm is proposed to allow microgrids merge or split self-adaptively based on NSGA-II. Simulation result shows that the proposed algorithm can find the Nash equilibrium of the upper level of the model and the optimal operation mode for multi-microgrid in the two-level game, which yields a reduction of 52.7% in coalition mode compared to noncooperation mode.
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