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The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2.Viruses 2020, 12, 428 2 of 11 origin and is 96% identical at the whole-genome level to a bat SARS-like coronavirus [22]. In addition, SARS-CoV-2 is also closely related to other SARS-like coronaviruses and shares a 79.5% sequence identity to SARS-CoV [22]. For some encoded proteins like coronavirus main proteinase (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), the sequence identity is even higher and can be as high as 96% between SARS-CoV-2 and SARS-CoV [23]. Therefore, it was thought that SARS-CoV-2 would function in a similar way to SARS-CoV in the human-infection and pathogenic mechanism [22][23][24].Coronaviruses use the surface spike (S) glycoprotein on the coronavirus envelope to attach host cells and mediate host cell membrane and viral membrane fusion during infection [25]. The spike protein includes two regions, S1 and S2, where S1 is for host cell receptor binding and S2 is for membrane fusion. The S1 region also includes an N-terminal domain (NTD) and three C-terminal domains (CTD1, CTD2, and CTD3) [26]. For SARS-CoV, the receptor binding domain (RBD) is located in the CTD1 of the S1 region. SARS-CoV attaches the human host cells through the binding of the RBD protein to the angiotensin-converting enzyme II (ACE2) [27,28]. Therefore, the interaction between RBD and ACE2 is a prerequisite for the human infection with SARS-CoV. Given the high homology between SARS-CoV and SARS-CoV-2, it was expected that SARS-CoV-2 would also use the ACE2 molecule as the receptor to enter human cells [24,29]. This hypothesis was further experimentally confirmed by the virus infectivity studies from the Shi group, in which SARS-CoV-2 is able to use the ACE2 proteins from humans, Chinese horseshoe bats, and civ...

Abstract-Emerging storage technologies such as flash memories, phase-change memories, and spin-transfer torque memories are poised to close the enormous performance gap between disk-based storage and main memory. We evaluate several approaches to integrating these memories into computer systems by measuring their impact on IO-intensive, database, and memory-intensive applications. We explore several options for connecting solid-state storage to the host system and find that the memories deliver large gains in sequential and random access performance, but that different system organizations lead to different performance trade-offs. The memories provide substantial application-level gains as well, but overheads in the OS, file system, and application can limit performance. As a result, fully exploiting these memories' potential will require substantial changes to application and system software. Finally, paging to fast non-volatile memories is a viable option for some applications, providing an alternative to expensive, powerhungry DRAM for supporting scientific applications with large memory footprints.