Mechanism of an RBM-targeted rabbit monoclonal antibody 9H1 neutralizing SARS-CoV-2.

The COVID-19 pandemic, caused by SARS-CoV-2, has led to over 750 million infections and 6.8 million deaths worldwide since late 2019. Due to the continuous evolution of SARS-CoV-2, many significant variants have emerged, creating ongoing challenges to the prevention and treatment of the pandemic. Therefore, the study of antibody responses against SARS-CoV-2 is essential for the development of vaccines and therapeutics. Here we perform single particle cryo-electron microscopy (cryo-EM) structure determination of a rabbit monoclonal antibody (RmAb) 9H1 in complex with the SARS-CoV-2 wild-type (WT) spike trimer. Our structural analysis shows that 9H1 interacts with the receptor-binding motif (RBM) region of the receptor-binding domain (RBD) on the spike protein and by directly competing with angiotensin-converting enzyme 2 (ACE2), it blocks the binding of the virus to the receptor and achieves neutralization. Our findings suggest that utilizing rabbit-derived mAbs provides valuable insights into the molecular interactions between neutralizing antibodies and spike proteins and may also facilitate the development of therapeutic antibodies and expand the antibody library.

Mechanism of a rabbit monoclonal antibody broadly neutralizing SARS-CoV-2 variants.

Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a large number of existing antibodies and vaccines ineffective against this variant. Therefore, it is urgent to develop efficient broad-spectrum neutralizing therapeutic drugs. Here we characterize a rabbit monoclonal antibody (RmAb) 1H1 with broad-spectrum neutralizing potency against Omicron sublineages including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3 and BA.4/5. Cryo-electron microscopy (cryo-EM) structure determination of the BA.1 spike-1H1 Fab complexes shows that 1H1 targets a highly conserved region of RBD and avoids most of the circulating Omicron mutations, explaining its broad-spectrum neutralization potency. Our findings indicate 1H1 as a promising RmAb model for designing broad-spectrum neutralizing antibodies and shed light on the development of therapeutic agents as well as effective vaccines against newly emerging variants in the future.

Surface ozone changes during the COVID-19 outbreak in China: An insight into the pollution characteristics and formation regimes of ozone in the cold season.

The countrywide lockdown in China during the COVID-19 pandemic provided a natural experiment to study the characteristics of surface ozone (O3). Based on statistical analysis of air quality across China before and during the lockdown, the tempo-spatial variations and site-specific formation regimes of wintertime O3 were analyzed. The results showed that the O3 pollution with concentrations higher than air quality standards could occur widely in winter, which had been aggravated by the emission reduction during the lockdown. On the national scale of China, with the significant decrease (54.03%) in NO2 level from pre-lockdown to COVID-19 lockdown, the maximum daily 8-h average concentration of O3 (MDA8h O3) increased by 39.43% from 49.05 to 64.22 µg/m3. This increase was comprehensively contributed by attenuated NOx suppression and favorable meteorological changes on O3 formation during the lockdown. As to the pollution states of different monitoring stations, surface O3 responded oppositely to the consistent decreased NO2 across China. The O3 levels were found to increase in the northern and central regions, but decrease in the southern region, where the changes in both meteorology (e.g. temperature drops) and precursors (reduced emissions) during the lockdown had diminished local O3 production. The spatial differences in NOx levels generally dictate the site-specific O3 formation regimes in winter, with NOx-titration/VOCs-sensitive regimes being dominant in northern and central China, while VOCs-sensitive/transition regimes being dominant in southern China. These findings highlight the influence of NOx saturation levels on winter O3 formation and the necessity of VOCs emission reductions on O3 pollution controls.

Source apportionment of PM2.5 and sulfate formation during the COVID-19 lockdown in a coastal city of southeast China.

Revealing the changes in chemical compositions and sources of PM2.5 is important for understanding aerosol chemistry and emission control strategies. High time-resolved characterization of water-soluble inorganic ions, elements, organic carbon (OC), and elemental carbon (EC) in PM2.5 was conducted in a coastal city of southeast China during the COVID-19 pandemic. The results showed that the average concentration of PM2.5 during the city lockdown (CLD) decreased from 46.2 µg m-3 to 24.4 µg m-3, lower than the same period in 2019 (PM2.5: 37.1 µg m-3). Concentrations of other air pollutants, such as SO2, NO2, PM10, OC, EC, and BC, were also decreased by 27.3%-67.8% during the CLD, whereas O3 increased by 28.1%. Although SO2 decreased from 4.94 µg m-3to 1.59 µg m-3 during the CLD, the concentration of SO42- (6.63 µg m-3) was comparable to that (5.47 µg m-3) during the non-lockdown period, which were attributed to the increase (16.0%) of sulfate oxidation rate (SOR). Ox (O3+NO2) was positively correlated with SO42-, suggesting the impacts of photochemical oxidation. A good correlation (R2 = 0.557) of SO42- and Fe and Mn was found, indicating the transition-metal ion catalyzed oxidation. Based on positive matrix factorization (PMF) analysis, the contribution of secondary formation to PM2.5 increased during the epidemic period, consisting with the increase of secondary organic carbon (SOC), while other primary sources including traffic, dust, and industry significantly decreased by 9%, 8.5%, and 8%, respectively. This study highlighted the comprehensive and nonlinear response of chemical compositions and formation mechanisms of PM2.5 to anthropogenic emissions control under relatively clean conditions.

Numerical study of COVID-19 spatial-temporal spreading in London.

A recent study reported that an aerosolized virus (COVID-19) can survive in the air for a few hours. It is highly possible that people get infected with the disease by breathing and contact with items contaminated by the aerosolized virus. However, the aerosolized virus transmission and trajectories in various meteorological environments remain unclear. This paper has investigated the movement of aerosolized viruses from a high concentration source across a dense urban area. The case study looks at the highly air polluted areas of London: University College Hospital (UCH) and King's Cross and St Pancras International Station (KCSPI). We explored the spread and decay of COVID-19 released from the hospital and railway stations with the prescribed meteorological conditions. The study has three key findings: the primary result is that the concentration of viruses decreases rapidly by a factor of 2-3 near the sources although the virus may travel from meters up to hundreds of meters from the source location for certain meteorological conditions. The secondary finding shows viruses released into the atmosphere from entry and exit points at KCSPI remain trapped within a small radial distance of < 50 m. This strengthens the case for the use of face coverings to reduce the infection rate. The final finding shows that there are different levels of risk at various door locations for UCH; depending on which door is used there can be a higher concentration of COVID-19. Although our results are based on London, since the fundamental knowledge processes are the same, our study can be further extended to other locations (especially the highly air polluted areas) in the world.

Impact of quarantine measures on chemical compositions of PM2.5 during the COVID-19 epidemic in Shanghai, China.

The COVID-19 epidemic broke out in Wuhan, Hubei in December 2019 and in January 2020 and was later transmitted to the entire country. Quarantine measures during Chinese New Year effectively alleviated the spread of the epidemic, but they simultaneously resulted in a decline in anthropogenic emissions from industry, transportation, and import and export of goods. Herein, we present the major chemical composition of non-refractory PM2.5 (NR-PM2.5) and the concentrations of gaseous pollutants in an urban site in Shanghai before and during the quarantine period of the COVID-19 epidemic, which was Jan. 8-23 and Jan. 24-Feb. 8, respectively. The observed results show that the reduction in PM2.5 can be mainly attributed to decreasing concentrations of nitrate and primary aerosols. Nitrate accounted for 37% of NR-PM2.5 before the quarantine period when there was no emission reduction. During the quarantine period, the nitrate concentration decreased by approximately 60%, which is attributed to a reduction in the NOx concentration. Ammonium, as the main balancing cation, showed an approximately 45% simultaneous decrease in concentration. The concentrations of chloride and hydrocarbon-like organic aerosols from primary emissions also declined due to limited human activities. By contrast, sulphate and oxygenated organic aerosols showed a slight decrease in concentration, with their contributions increasing to 27% and 18%, respectively, during the quarantine period, which resulted in two pollution episodes with PM2.5 exceeding 100 µg/m3. This study provides a better understanding of the impact of quarantine measures on variations of the PM2.5 concentration and chemical compositions. Atmospheric oxidation capacities based on the oxidant (Ox = O3 + NO2) and oxidation ratios have been discussed for elucidating the source and formation of haze in an environment with lower anthropogenic emissions. With increasing contribution of secondary aerosols, lower NOx and nitrate concentrations did not completely avoid haze in Shanghai during the epidemic.