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1. Inactivation of Coronaviruses and Phage Phi6 from Irradiation across UVC Wavelengths

   https://doi.org/10.1021/acs.estlett.1c00178  

   Ma, Ben ; Linden, Yarrow S. ; Gundy, Patricia M. ; Gerba, Charles P. ; Sobsey, Mark D. ; Linden, Karl G. ( March 2021 , Environmental Science & Technology Letters)

   null (Ed.)

   Ultraviolet (UV) devices emitting UVC irradiation (200− 280 nm) have proven to be effective for virus disinfection, especially on surfaces and in air, due to their rapid effectiveness and limited to no material corrosion. Numerous studies of UV-induced inactivation focused on nonenveloped viruses. Little is known about UVC action on enveloped viruses across UVC wavelengths. In this study, we determined inactivation efficiencies of two coronaviruses (ssRNA) and an enveloped dsRNA bacteriophage surrogate in buffered aqueous solution (pH 7.4) using five commonly available UVC devices that uniquely emit light at different wavelengths spanning 222 nm emitting krypton chloride (KrCl*) excimers to 282 nm emitting UVC LEDs. Our results show that enveloped viruses can be effectively inactivated using UVC devices, among which the KrCl* excimer had the best disinfection performance (i.e., highest inactivation rate) for all three enveloped viruses. The coronaviruses exhibited similar sensitivities to UV irradiation across the UVC range, whereas the bacteriophage surrogate was much more resistant and exhibited significantly higher sensitivity to the Far UVC (<230 nm) irradiation. This study provides necessary information and guidance for using UVC devices for enveloped virus disinfection, which may help control virus transmission in public spaces during the ongoing COVID-19 pandemic and beyond. 

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2. Systematic evaluating and modeling of SARS-CoV-2 UVC disinfection

   https://doi.org/10.1038/s41598-022-09930-2  

   Freeman, Sebastian ; Kibler, Karen ; Lipsky, Zachary ; Jin, Sha ; German, Guy K. ; Ye, Kaiming ( December 2022 , Scientific Reports)

   Abstract The ongoing COVID-19 global pandemic has necessitated evaluating various disinfection technologies for reducing viral transmission in public settings. Ultraviolet (UV) radiation can inactivate pathogens and viruses but more insight is needed into the performance of different UV wavelengths and their applications. We observed greater than a 3-log reduction of SARS-CoV-2 infectivity with a dose of 12.5 mJ/cm 2 of 254 nm UV light when the viruses were suspended in PBS, while a dose of 25 mJ/cm 2 was necessary to achieve a similar reduction when they were in an EMEM culture medium containing 2%(v/v) FBS, highlighting the critical effect of media in which the virus is suspended, given that SARS-CoV-2 is always aerosolized when airborne or deposited on a surface. It was found that SARS-CoV-2 susceptibility (a measure of the effectiveness of the UV light) in a buffer such as PBS was 4.4-fold greater than that in a cell culture medium. Furthermore, we discovered the attenuation of UVC disinfection by amino acids, vitamins, and niacinamide, highlighting the importance of determining UVC dosages under a condition close to aerosols that wrap the viruses. We developed a disinfection model to determine the effect of the environment on UVC effectiveness with three different wavelengths, 222 nm, 254 nm, and 265 nm. An inverse correlation between the liquid absorbance and the viral susceptibility was observed. We found that 222 nm light was most effective at reducing viral infectivity in low absorbing liquids such as PBS, whereas 265 nm light was most effective in high absorbing liquids such as cell culture medium. Viral susceptibility was further decreased in N95 masks with 222 nm light being the most effective. The safety of 222 nm was also studied. We detected changes to the mechanical properties of the stratum corneum of human skins when the 222 nm accumulative exposure exceeded 50 J/cm 2 .The findings highlight the need to evaluate each UV for a given application, as well as limiting the dose to the lowest dose necessary to avoid unnecessary exposure to the public. 

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3. Evaluation of parameters governing dark and photo-repair in UVC-irradiated Escherichia coli

   https://doi.org/10.1039/d1ew00644d  

   Maghsoodi, Mostafa ; Lowry, Grace L. ; Smith, Ian M. ; Snow, Samuel D. ( February 2022 , Environmental Science: Water Research & Technology)

   After decades of UV disinfection practice and numerous studies on the potential for pathogens to undergo dark or photo-repair after UV exposure, recent advances in UV light emitting diode (LED) technologies prompt renewed attention to bacterial reactivation and regrowth processes after UV exposure. The aspect of photorepair conditions warrants particular attention, because even studies on conventional mercury vapor lamps have not sufficiently characterized these parameters. Wastewater encounters a wide range of environmental conditions upon discharge ( e.g. , solar irradiation and dissolved organics) which may affect repair processes and ultimately lead to overestimations of pathogen removal. Escherichia coli was used here to investigate the impacts of changing reactivation conditions after UV 254 and UV 278 irradiation. UV 254 and UV 278 doses of 13.75 ± 0.4 mJ cm −2 and 28.3 ± 0.8 mJ cm −2 were required to induce a 3.0 log inactivation of E. coli , respectively. Specifically, photoreactivation conditions were varied across dissolved organic matter (DOM) content and photoreactivation wavelengths and intensities. Photoreactivation achieved higher log recoveries than dark repair, ranging from 0.8 to 1.8 log differences, but a secondary disinfection effect occurred under UVA irradiation. During photoreactivation, humic acid inhibited the initial repair of UV 278 -dosed E. coli , but culture media enhanced recovery for both dosage wavelengths. Photoreactivation profiles under UV 395 , UV 365 , and visible light depended on both fluence and time, with more regrowth observed upon exposure to visible light and the least under 365 nm. The susceptibility of E. coli to UVA was increased by prior exposure to UVC. 

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4. A Multifunctional Neutralizing Antibody‐Conjugated Nanoparticle Inhibits and Inactivates SARS‐CoV‐2

   https://doi.org/10.1002/advs.202103240  

   Cai, Xiaolei ; Chen, Min ; Prominski, Aleksander ; Lin, Yiliang ; Ankenbruck, Nicholas ; Rosenberg, Jillian ; Nguyen, Mindy ; Shi, Jiuyun ; Tomatsidou, Anastasia ; Randall, Glenn ; et al ( November 2021 , Advanced Science)

   The outbreak of 2019 coronavirus disease (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has resulted in a global pandemic. Despite intensive research, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS‐CoV‐2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high‐affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS‐CoV‐2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS‐CoV‐2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS‐CoV‐2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS‐CoV‐2 and its variants.

    

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5. Multicellular spatial model of RNA virus replication and interferon responses reveals factors controlling plaque growth dynamics

   https://doi.org/10.1371/journal.pcbi.1008874  

   Aponte-Serrano, Josua O. ; Weaver, Jordan J. ; Sego, T. J. ; Glazier, James A. ; Shoemaker, Jason E. ( October 2021 , PLOS Computational Biology)

   Kosakovsky Pond, Sergei L. (Ed.)

   Respiratory viruses present major public health challenges, as evidenced by the 1918 Spanish Flu, the 1957 H2N2, 1968 H3N2, and 2009 H1N1 influenza pandemics, and the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Severe RNA virus respiratory infections often correlate with high viral load and excessive inflammation. Understanding the dynamics of the innate immune response and its manifestations at the cell and tissue levels is vital to understanding the mechanisms of immunopathology and to developing strain-independent treatments. Here, we present a novel spatialized multicellular computational model of RNA virus infection and the type-I interferon-mediated antiviral response that it induces within lung epithelial cells. The model is built using the CompuCell3D multicellular simulation environment and is parameterized using data from influenza virus-infected cell cultures. Consistent with experimental observations, it exhibits either linear radial growth of viral plaques or arrested plaque growth depending on the local concentration of type I interferons. The model suggests that modifying the activity of signaling molecules in the JAK/STAT pathway or altering the ratio of the diffusion lengths of interferon and virus in the cell culture could lead to plaque growth arrest. The dependence of plaque growth arrest on diffusion lengths highlights the importance of developing validated spatial models of cytokine signaling and the need for in vitro measurement of these diffusion coefficients. Sensitivity analyses under conditions leading to continuous or arrested plaque growth found that plaque growth is more sensitive to variations of most parameters and more likely to have identifiable model parameters when conditions lead to plaque arrest. This result suggests that cytokine assay measurements may be most informative under conditions leading to arrested plaque growth. The model is easy to extend to include SARS-CoV-2-specific mechanisms or to use as a component in models linking epithelial cell signaling to systemic immune models. 

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