a b s t r a c tOne of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses. ADE modulates the immune response and can elicit sustained inflammation, lymphopenia, and/or cytokine storm, one or all of which have been documented in severe cases and deaths. ADE also requires prior exposure to similar antigenic epitopes, presumably circulating in local viruses, making it a possible explanation for the observed geographic limitation of severe cases and deaths.
DNA aptamers were developed against murine norovirus (MNV) using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Nine rounds of SELEX led to the discovery of AG3, a promising aptamer with very high affinity for MNV as well as for lab-synthesized capsids of a common human norovirus (HuNoV) outbreak strain (GII.3). Using fluorescence anisotropy, AG3 was found to bind with MNV with affinity in the low picomolar range. The aptamer could cross-react with HuNoV though it was selected against MNV. As compared to a non-specific DNA control sequence, the norovirus-binding affinity of AG3 was about a million-fold higher. In further tests, the aptamer also showed nearly a million-fold higher affinity for the noroviruses than for the feline calicivirus (FCV), a virus similar in size and structure to noroviruses. AG3 was incorporated into a simple electrochemical sensor using a gold nanoparticle-modified screen-printed carbon electrode (GNPs-SPCE). The aptasensor could detect MNV with a limit of detection of approximately 180 virus particles, for possible on-site applications. The lead aptamer candidate and the aptasensor platform show promise for the rapid detection and identification of noroviruses in environmental and clinical samples.
Enteric and respiratory viruses are among the most frequent causes of human infections, and hands play an important role in the spread of these and many other viral diseases. Regular and proper hand hygiene by caregivers and food handlers in particular is essential to decontaminate hands and potentially interrupt such spread. What would be considered a proper decontamination of hands? Handwashing with regular soap and water is often considered sufficient, but what of hygienic handwash and handrub antiseptic products? Are they more effective? The evidence suggests that some clearly are. Activity against bacteria may not reflect the ability of hygienic hand antiseptics to deal with viruses, especially those that are nonenveloped. In spite of the acknowledged importance of hands as vehicles for viruses, there is a lack of suitable regulatory mechanism for handwash or handrub products to make claims of efficacy against viruses. This is in contrast with the ability of general-purpose disinfectants to make antiviral claims, although transmission of viruses from surfaces other than those of reusable medical devices may play only a minor role in virus transmission. This review discusses the (1). recent information on the relative importance of viruses as human pathogens, particularly those causing enteric and respiratory infections; (2). the survival of relevant viruses on human hands in comparison with common gram-negative and gram-positive bacteria; (3). the potential of hands to transfer or receive such contamination on casual contact; (4). role of hands in the spread of viruses; (5). the potential of hygienic measures to eliminate viruses from contaminated hands; (6). relative merits of available protocols to assess the activity of hygienic hand antiseptics against viruses; and (7). factors considered crucial in any tests to assess the activity of hygienic hand antiseptics against viruses. In addition, this review proposes surrogate viruses in such testing and discusses issues for additional consideration by researchers, manufacturers, end-users, and regulators.
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