Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first 6 months of the COVID-19 pandemic.

Understanding the molecular evolution of the SARS-CoV-2 virus as it continues to spread in communities around the globe is important for mitigation and future pandemic preparedness. Three-dimensional structures of SARS-CoV-2 proteins and those of other coronavirusess archived in the Protein Data Bank were used to analyze viral proteome evolution during the first 6 months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48 000 viral isolates revealed how each one of 29 viral proteins have undergone amino acid changes. Catalytic residues in active sites and binding residues in protein-protein interfaces showed modest, but significant, numbers of substitutions, highlighting the mutational robustness of the viral proteome. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for potential drug discovery targets and the four structural proteins that comprise the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and protein-protein and protein-nucleic acid interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first six months of the COVID-19 pandemic.

Three-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48,000 viral proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed that most substitutions map to protein surfaces and boundary layers with a minority affecting hydrophobic cores. Conservative changes were observed more frequently in cores versus boundary layers/surfaces. Active sites and protein-protein interfaces showed modest numbers of substitutions. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for six drug discovery targets and four structural proteins comprising the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and functional interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

Airborne dust and allergen generation during dusting with and without spray polish.

BACKGROUND: Dusting is a commonly used method for dust removal from surfaces in the home. However, the process of dusting may contribute to airborne dust levels by disturbing dust particles from a surface and failing to remove it from the indoor environment. OBJECTIVE: We sought to measure the quantity of allergen-laden dust disturbed into the air during dusting and discover whether applying spray polish to either the dusty surface or the cleaning cloth reduced this amount. METHODS: A common furniture polish was tested for its ability to prevent dust particles and major house dust mite (Der p 1) or major cat (Fel d 1) allergen from becoming airborne during dusting. Tests were completed with a repeatable mechanized dusting procedure with polish sprayed onto either a cleaning cloth or directly onto a surface, and this was compared with a control procedure with a standard duster. Airborne dust was measured with an air-particle counter and by means of anti-Der p 1 or anti-Fel d 1 ELISA. RESULTS: Considerable quantities of dust became airborne during dusting. When polish was sprayed onto the cleaning cloth, the concentration of airborne dust particles was reduced by a mean of 83.4%, house dust mite allergen by 50.3%, and cat allergen by 57.4% when compared with dry-cloth controls. Spraying polish directly onto the surface was even more effective at reducing the generation of airborne particles (92.9%) and allergens (Der p 1 by > or =95% to below the sensitivity of the ELISA and Fel d 1 by 95%). All reductions were significant when compared with dry-cloth controls (P <.01, Mann-Whitney U test). CONCLUSIONS: This study showed that application of a polish spray to either the surface or the cloth during dusting greatly reduced dust and allergen evolution into the air, which should reduce exposure to airborne allergens in the home.