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Abstract Background Non-enveloped viruses, which lack a lipid envelope, display higher resistance to disinfectants, soaps and sanitizers compared to enveloped viruses. The capsids of these viruses are highly stable and symmetric protein shells that resist inactivation by commonly employed virucidal agents. This group of viruses include highly transmissible human pathogens such as Rotavirus, Poliovirus, Foot and Mouth Disease Virus, Norovirus and Adenovirus; thus, devising appropriate strategies for chemical disinfection is essential. Results In this study, we tested a mild, hypoallergenic combination of a denaturant, alcohol, and organic acid (3.2% citric acid, 1% urea and 70% ethanol, pH4) on two representative non-enveloped viruses – Human Adenovirus 5 (HAdV5) and Feline Calicivirus (FCV)– and evaluated the pathways of capsid neutralization using biophysical methods. The conformational shifts in the capsid upon chemical treatment were studied using Differential Scanning Calorimetry (DSC), while the morphological alterations were visualized concurrently using Transmission Electron Microscopy (TEM). We found that while treatment of purified HAdV5 particles with a formulation resulted in thermal instability and, large scale aggregation; similar treatment of FCV particles resulted in complete collapse of the capsids. Further, while individual components of the formulation caused significant damage to the capsids, a synergistic action of the whole formulation was evident against both non-enveloped viruses tested. Conclusions The distinct effects of the chemical treatment on the morphology of HAdV5 and FCV suggests that non-enveloped viruses with icosahedral geometry can follow different morphological pathways to inactivation. Synergistic effect of whole formulation is more effective compared to individual components. Molecular level understanding of inactivation pathways may result in the design and development of effective mass-market formulations for rapid neutralization of non-enveloped viruses.

Abstract The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has highlighted the threat that viral outbreaks pose to global health. A key tool in the arsenal to prevent and control viral disease outbreaks is disinfection of equipment and surfaces with formulations that contain virucidal agents (VA). However, assessment of the efficacy of virus inactivation often requires live virus assays or surrogate viruses such as Modified Vaccinia Virus Ankara (MVA), which can be expensive, time consuming and technically challenging. Therefore, we have developed a pseudo-typed virus (PV) based approach to assess the inactivation of enveloped viruses with a fast and quantitative output that can be adapted to emerging viruses. Additionally, we have developed a method to completely remove the cytotoxicity of virucidal agents while retaining the required sensitivity to measure PV infectivity. Our results indicated that the removal of cytotoxicity was an essential step to accurately measure virus inactivation. Further, we demonstrated that there was no difference in susceptibility to virus inactivation between PVs that express the envelopes of HIV-1, SARS-CoV-2, and Influenza A/Indonesia. Therefore, we have developed an effective and safe alternative to live virus assays that enables the rapid assessment of virucidal activity for the development and optimization of virucidal reagents.

Objectives: Early in the COVID-19 pandemic, global health authorities identified and emphasized the importance of practicing proper hand hygiene to reduce the transmission of SARS-CoV-2 and to diminish the chances of becoming infected. It is well established in the scientific literature that surfactants and alcohols are capable of inactivating enveloped viruses such as SARS-CoV-2. However, given the novel nature of the virus, Unilever adopted an evidence-based approach to demonstrate virucidal efficacy of marketed bar soaps, liquid handwashes, and alcohol-based hand sanitizers against the original and selected variants of SARS-CoV-2. Methods: High titers of clinically isolated and laboratory-propagated SARS-CoV-2 strains were subjected to a range of selected proprietary formulations from Unilever at end-user–relevant dilutions, temperature, and contact duration, and were tested according to the internationally recognized ASTM E-1052 test protocol. Results: All tested personal-care formulations were effective against the parental SARS-CoV-2 strain as well as the β (beta) and δ (delta) variants of concern. More specifically, bar soaps with a varying concentration of total fatty matter content and liquid handwashes with varying levels of total surfactants reduced the viral titer by >99.9% within 20 seconds. Alcohol-based hand sanitizers demonstrated >99.99% reduction of input viral load within 15 seconds of contact with the viral inoculum. Conclusions: In conclusion, we have provided empirical proof that well-designed personal-care formulations that act through generic physicochemical mechanism against the basic structure of the virus particle have high virucidal efficacy against the original and evolved SARS-CoV-2 variants. Furthermore, we argue that due to the broad-spectrum mode of action of these tested formulations, the continued practice of good hand hygiene practices with everyday products holds significant promise as an easily accessible, economic, and effective nontherapeutic public health intervention toward reducing the transmission of present and future variants of SARS-CoV-2 across communities and populations.

Despite considerable progress being made on vaccine roll out, practicing proper hand hygiene has been advocated as a consistent precautionary intervention against the circulating and emerging variants of SARS-CoV-2. Two variants of concern, namely beta and delta, have been shown to exhibit enhanced transmissibility, high viral load, and ability to escape antibody-mediated neutralization. In this report we have empirically determined the efficacy of selected personal care formulations from Unilever in inactivating the beta and delta variants of SARS-CoV-2 under simulated real-life conditions. All the formulations demonstrated greater than 99.9% reduction in viral infective titres which is comparable to inactivation of the original strain of SARS-CoV-2 virus tested under the same conditions. Therefore, it can be concluded that well-designed personal care formulations when tested under consumer-centric conditions, and with proven efficacy against the parent strain of SARS-CoV-2 will continue to be effective against extant and emerging variants of SARS-CoV-2.

Murine models of human genetic disorders provide a valuable tool for investigating the scope for application of induced pluripotent stem cells (iPSC). Here we present a proof-of-concept study to demonstrate generation of iPSC from a mouse model of X-linked chronic granulomatous disease (X-CGD), and their successful differentiation into haematopoietic progenitors of the myeloid lineage. We further demonstrate that additive gene transfer using lentiviral vectors encoding gp91(phox) is capable of restoring NADPH-oxidase activity in mature neutrophils derived from X-CGD iPSC. In the longer term, correction of iPSC from human patients with CGD has therapeutic potential not only through generation of transplantable haematopoietic stem cells, but also through production of large numbers of autologous functional neutrophils.