Gold nanoparticles in virus detection: Recent advances and potential considerations for SARS-CoV-2 testing development

Abstract Viruses are infectious agents that pose significant threats to plants, animals, and humans. The current coronavirus disease 2019 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally and resulted in over 2 million deaths and immeasurable financial losses. Rapid and sensitive virus diagnostics become crucially important in controlling the spread of a pandemic before effective treatment and vaccines are available. Gold nanoparticle (AuNP)-based testing holds great potential for this urgent unmet biomedical need. In this review, we describe the most recent advances in AuNP-based viral detection applications. In addition, we discuss considerations for the design of AuNP-based SARS-CoV-2 testings. Finally, we highlight and propose important parameters to consider for the future development of effective AuNP-based testings that would be critical for not only this COVID-19 pandemic, but also potential future outbreaks. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing

Simultaneous enrichment and separation of neutral and sialyl glycopeptides of SARS-CoV-2 spike protein enabled by dual-functionalized Ti-IMAC material.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a serious threat to human health all over the world. The development of effective vaccines has been focusing on the spike (S) glycoprotein, which mediates viral invasion to human cells through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor. In this work, we perform analytical characterization of N- and O-linked glycosylation of the SARS-CoV-2 S glycoprotein. We explore the novel use of dual-functionalized titanium (IV)-immobilized metal affinity chromatography (Ti-IMAC) material for simultaneous enrichment and separation of neutral and sialyl glycopeptides of a recombinant SARS-CoV-2 S glycoprotein from HEK293 cells. This strategy helps eliminate signal suppression from neutral glycopeptides for the detection of sialyl glycopeptides and improves the glycoform coverage of the S protein. We profiled 19 of its 22 potential N-glycosylated sites with 398 unique glycoforms using the dual-functional Ti-IMAC approach, which exhibited improvement of coverage by 1.6-fold compared to the conventional hydrophilic interaction chromatography (HILIC) glycopeptide enrichment method. We also identified O-linked glycosylation site that was not found using the conventional HILIC approach. In addition, we reported on the identification of mannose-6-phosphate (M6P) glycosylation, which substantially expands the current knowledge of the spike protein's glycosylation landscape and enables future investigation into the influence of M6P glycosylation of the spike protein on its cell entry.

Discovery of anti-infective adipostatins through bioactivity-guided isolation and heterologous expression of a type III polyketide synthase.

Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.

Spatial and temporal variation characteristics of atmospheric NO2 and SO2 in the Beijing-Tianjin-Hebei region before and after the COVID-19 outbreak.

Emergency response mechanisms were activated throughout China during the COVID-19 outbreak. It is different from the temporary, partial, and limited pollution control measures taken to ensure the regional environmental quality during several important events such as the 2008 Beijing Olympic Games and the 2014 Asia-Pacific Economic Cooperation (APEC). During the COVID-19 epidemic period, extensive movement of people and almost all unnecessary industrial production (necessary industrial production refers to the production of food, epidemic prevention materials, etc.) have been severely restricted, so transportation and industrial production have been greatly reduced. This is a rare extreme emission reduction scenario that presents a unique opportunity for atmospheric research. In this study, based on hourly mass concentration data of NO2 and SO2 from atmospheric monitoring sites in the Beijing-Tianjin-Hebei (BTH) region during the COVID-19 epidemic period, the changes in transportation and industrial production in the region, data statistics, and spatial analysis were used to analyze the pollution changes and their causes. The results indicate that the NO2 and SO2 concentrations in the BTH region decreased significantly during the epidemic period. The spatial distribution pattern of NO2 pollution in the BTH region was "high in the southeast and low in the northwest," and SO2 pollution in the BTH region was high in the southern and eastern parts of Hebei. The initiation of emergency response level 1 had an obvious effect on reducing NO2 and SO2 pollution in the region, while the impact of emergency response level 2 and below was limited. Compared with the single traffic control, the comprehensive control, similar to the emergency response, had a better effect on reducing NO2 pollution in the region. The control of major large cities in the region also had a certain effect on alleviating NO2 and SO2 pollution in the entire region. Moreover, for activities under short-term control, it is particularly important to guard against the "retaliatory growth" after the control is lifted. By reducing and controlling some polluting industries in industrial production, the degree of NO2 and SO2 pollution in the region can be effectively reduced. The manufacturing industry of chemical raw materials and the chemical products and non-metallic mineral products industry made a great contribution to the change in industrial source pollution emissions in the BTH region during the COVID-19 epidemic. Road traffic emissions remained an important source of NO2 emissions in the BTH region during this period. NO2 emission reduction can be effectively achieved by controlling road traffic and transportation.

[Analysis of Changes and Factors Influencing Air Pollutants in the Beijing-Tianjin-Hebei Region During the COVID-19 Pandemic].

A series of strict control measures were imposed in the Beijing-Tianjin-Hebei region in early 2020 to control the spread of COVID-19. These measures have led to a reduction of anthropogenic air pollutants, providing an opportunity to observe the contribution of human activities to local air pollution. In this study, the control period was divided into four stages:the before, early, middle, and later stages. Based on a variety of data including meteorological, traffic, and industrial manufacturing datasets, statistical methods were combined with spatial analysis to evaluate changes in air pollution and associated human impacts during each stage. In addition, suggestions are made for further regional air pollution control in the Beijing-Tianjin-Hebei area. Key results are as follows:① Overall, the AQI and the concentrations of six air pollutants, especially SO2, PM10, and NO2, were lower during control period than during the equivalent period in 2019 (reductions of 26.5%, 24.3%, and 16.9%, respectively). From the before to later stages, pollutants (except O3) showed a downward trend while O3 increased significantly during the before stage (by 76.2%) and the growth rate slowed during the middle and later stages; ②During the prior stage, Beijing experienced two periods with heavy air pollution days as a result of the local accumulation of pollutants, secondary transformation, and regional transport. The concentration of PM2.5 in February was nearly 60% lower than in February 2014 under similar meteorological conditions in Beijing; ③ Following an increase in traffic volume and industrial activity, changes in air pollutants tended to be stable or slightly increase during the middle and later stages of the control period. The grey relation coefficients between thermal radiation intensity anomalies and the main pollutants in heavy industrial cities were greater than 0.6, which means that the control of industrial emissions remains key to controlling air pollution.