Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R₀ through specific transmission control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R₀ multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development.

Using X-ray free-electron lasers (XFELs), it is possible to determine three-dimensional structures of nanoscale particles using single-particle imaging methods. Classification algorithms are needed to sort out the single-particle diffraction patterns from the large amount of XFEL experimental data. However, different methods often yield inconsistent results. This study compared the performance of three classification algorithms: convolutional neural network, graph cut and diffusion map manifold embedding methods. The identified single-particle diffraction data of the PR772 virus particles were assembled in the three-dimensional Fourier space for real-space model reconstruction. The comparison showed that these three classification methods lead to different datasets and subsequently result in different electron density maps of the reconstructed models. Interestingly, the common dataset selected by these three methods improved the quality of the merged diffraction volume, as well as the resolutions of the reconstructed maps.

Cryptochromes are blue light receptors that mediate circadian rhythm and magnetic sensing in various organisms. A typical cryptochrome consists of a conserved photolyase homology region domain and a varying carboxyl-terminal extension across species. The structure of the flexible carboxyl-terminal extension and how carboxyl-terminal extension participates in cryptochrome’s signaling function remain mostly unknown. In this study, we uncover the potential missing link between carboxyl-terminal extension conformational changes and downstream signaling functions. Specifically, we discover that the blue-light induced opening of carboxyl-terminal extension in C. reinhardtii animal-like cryptochrome can structurally facilitate its interaction with Rhythm Of Chloroplast 15, a circadian-clock-related protein. Our finding is made possible by two technical advances. Using single-molecule Förster resonance energy transfer technique, we directly observe the displacement of carboxyl-terminal extension by about 15 Å upon blue light excitation. Combining structure prediction and solution X-ray scattering methods, we propose plausible structures of full-length cryptochrome under dark and lit conditions. The structures provide molecular basis for light active conformational changes of cryptochrome and downstream regulatory functions.

HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 Å using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 Å using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140–153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.

Serial crystallography (SX), first used as an application of X-ray free-electron lasers (XFELs), is becoming a useful method to determine atomic-resolution structures of proteins from micrometer-sized crystals with bright X-ray sources. Because of unknown orientations of crystals in SX, indexing ambiguity issue arises when the symmetry of Bravais lattice is higher than the space group symmetry, making some diffraction signals wrongly merged to the total intensity in twinned orientations. In this research, we developed a program within the CrystFEL framework, the EM-detwin, to resolve this indexing ambiguity problem based on the expectation-maximization algorithm. Testing results on the performance of the EM-detwin have demonstrated its usefulness in correctly indexing diffraction data as a valuable tool for SX data analysis.