Changes in aerosol loading before, during and after the COVID-19 pandemic outbreak in China: Effects of anthropogenic and natural aerosol.

Anthropogenic emissions reduced sharply in the short-term during the coronavirus disease pandemic (COVID-19). As COVID-19 is still ongoing, changes in atmospheric aerosol loading over China and the factors of their variations remain unclear. In this study, we used multi-source satellite observations and reanalysis datasets to synergistically analyze the spring (February-May) evolution of aerosol optical depth (AOD) for multiple aerosol types over Eastern China (EC) before, during and after the COVID-19 lockdown period. Regional meteorological effects and the radiative response were also quantitatively assessed. Compared to the same period before COVID-19 (i.e., in 2019), a total decrease of -14.6 % in tropospheric TROPOMI nitrogen dioxide (NO2) and a decrease of -6.8 % in MODIS AOD were observed over EC during the lockdown period (i.e., in 2020). After the lockdown period (i.e., in 2021), anthropogenic emissions returned to previous levels and there was a slight increase (+2.3 %) in AOD over EC. Moreover, changes in aerosol loading have spatial differences. AOD decreased significantly in the North China Plain (-14.0 %, NCP) and Yangtze River Delta (-9.4 %) regions, where anthropogenic aerosol dominated the aerosol loading. Impacted by strong wildfires in Southeast Asia during the lockdown period, carbonaceous AOD increased by +9.1 % in South China, which partially offset the emission reductions. Extreme dust storms swept through the northern region in the period after COVID-19, with an increase of +23.5 % in NCP and + 42.9 % in Northeast China (NEC) for dust AOD. However, unfavorable meteorological conditions overwhelmed the benefits of emission reductions, resulting in a +20.1 % increase in AOD in NEC during the lockdown period. Furthermore, the downward shortwave radiative flux showed a positive anomaly due to the reduced aerosol loading in the atmosphere during the lockdown period. This study highlights that we can benefit from short-term controls for the improvement of air pollution, but we also need to seriously considered the cross-regional transport of natural aerosol and meteorological drivers.

A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding.

The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our in-vitro biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases.

An engineered 5-helix bundle derived from SARS-CoV-2 S2 pre-binds sarbecoviral spike at both serological- and endosomal-pH to inhibit virus entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related sarbecoviruses enter host cells by receptor-recognition and membrane-fusion. An indispensable step in fusion is the formation of 6-helix bundle by viral spike heptad repeats 1 and 2 (HR1 and HR2). Here, we report the construction of 5-helix bundle (5HB) proteins for virus infection inhibition. The optimal construct inhibits SARS-CoV-2 pseudovirus entry with sub-micromolar IC50. Unlike HR2-based peptides that cannot bind spike in the pre-fusion conformation, 5HB features with the capability of binding to pre-fusion spike. Furthermore, 5HB binds viral HR2 at both serological- and endosomal-pH, highlighting its entry-inhibition capacity when SARS-CoV-2 enters via either cell membrane fusion or endosomal route. Finally, we show that 5HB could neutralize S-mediated entry of the predominant SARS-CoV-2 variants and a wide spectrum of sarbecoviruses. These data provide proof-of-concept evidence that 5HB might be developed for the prevention and treatment of SARS-CoV-2 and other emerging sarbecovirus infections.

S19W, T27W, and N330Y mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis.

SARS-CoV-2 recognizes, via its spike receptor-binding domain (S-RBD), human angiotensin-converting enzyme 2 (ACE2) to initiate infection. Ecto-domain protein of ACE2 can therefore function as a decoy. Here we show that mutations of S19W, T27W, and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding. Y330 could be synergistically combined with either W19 or W27, whereas W19 and W27 are mutually unbeneficial. The structures of SARS-CoV-2 S-RBD bound to the ACE2 mutants reveal that the enhanced binding is mainly contributed by the van der Waals interactions mediated by the aromatic side-chains from W19, W27, and Y330. While Y330 and W19/W27 are distantly located and devoid of any steric interference, W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts, explaining their incompatibility. Finally, using pseudotyped SARS-CoV-2 viruses, we demonstrate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses. Taken together, our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W, T27W, and N330Y mutations in ACE2, paving the way for potential application of these mutants in clinical treatment of COVID-19.