Molecular dynamics (MD) simulations are employed to study biaxial stretch-induced crystallization of polymers, during which the individual roles of chain conformation and orientation on crystal nucleation and growth are clarified. Systems with different stiffness and orientations are constructed by changing the stretch ratios of the x-and y-axis, which allow us to figure out the individual contributions of chain conformation and orientation to flowenhanced nucleation. The results show that nucleation occurs in areas with high segment orientation, and the higher orientation corresponds to the shorter nucleation induction period. The relationship between the nucleation induction period and orientation is quantitatively expressed, which indicates that orientation plays a dominant role in flow-enhanced nucleation. On the other hand, the results show that chain stiffness exhibits a negative correlation with nucleation in biaxial stretch, supporting that conformational entropy reduction is not the main driving force in flow-induced crystallization of polymers. With the secondary nucleation model, the crystal growth rates in different directions correlate well with the orientation at the growth front of the clusters, further confirming the decisive role of orientation in crystal nucleation and growth. Finally, crystal cluster merging is proposed to be a way to form shish structures in highly oriented melts.

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The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19.