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• Journal article
  Scott C, Kankanala J, Foster TL, Goldhill DH, Bao P, Simmons K, Pingen M, Bentham M, Atkins E, Loundras E, Eldertield R, Claridge JK, Thompson J, Stilwell PR, Tathineni R, McKimmie CS, Targett-Adams P, Schnell JR, Cook GP, Evans S, Barclay WS, Foster R, Griffin Set al., 2020,

  Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza

  , PLOS PATHOGENS, Vol: 16, ISSN: 1553-7366
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  • Citations: 4
• Journal article
  Sanchez-David RY, Swann OC, Peacock TP, Barclay WSet al., 2020,

  ACE2: The Only Thing That Matters?

  , AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 161-163, ISSN: 1073-449X
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  • Citations: 3
• Journal article
  McKay PF, Hu K, Blakney AK, Samnuan K, Brown JC, Penn R, Zhou J, Bouton CR, Rogers P, Polra K, Lin PJC, Barbosa C, Tam YK, Barclay WS, Shattock RJet al., 2020,

  Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

  , Nature Communications, Vol: 11, Pages: 1-7, ISSN: 2041-1723

  The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.

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• Journal article
  Zhou J, Otter JA, Price JR, Cimpeanu C, Garcia DM, Kinross J, Boshier PR, Mason S, Bolt F, Holmes AH, Barclay WSet al., 2020,

  Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London

  , Clinical Infectious Diseases, Vol: 2020, Pages: 1-1, ISSN: 1058-4838

  BACKGROUND: Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London. METHODS: We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114/218 (52.3%) of surfaces and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.

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• Journal article
  Rodriguez-Manzano J, Malpartida-Cardenas K, Moser N, Pennisi I, Cavuto M, Miglietta L, Moniri A, Penn R, Satta G, Randell P, Davies F, Bolt F, Barclay W, Holmes A, Georgiou Pet al., 2020,

  A handheld point-of-care system for rapid detection of SARS-CoV-2 in under 20 minutes

  <jats:title>Abstract</jats:title><jats:p>The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (&lt; 20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 90.55% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 ± 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n=40), showing average detection times of 12.89 ± 2.59 min for positive samples (n=34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geo-localization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.</jats:p><jats:sec><jats:title>One Sentence Summary</jats:title><jats:p>We demonstrate isothermal detection of SARS-CoV-2 in under 20 minutes from extracted RNA samples with a handheld Lab-on-Chip platform.</jats:p></jats:sec>

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• Journal article
  Peacock TP, Swann OC, Salvesen HA, Staller E, Leung PB, Goldhill DH, Zhou H, Lillico SG, Whitelaw CBA, Long JS, Barclay WSet al., 2020,

  Swine ANP32A supports avian influenza virus polymerase.

  , Journal of Virology, Vol: 94, ISSN: 0022-538X

  Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as 'mixing vessels', being susceptible to both avian and human origin viruses, which allows the emergence of novel reassortants, such as the precursor to the 2009 H1N1 pandemic. ANP32 proteins are host factors that act as influenza virus polymerase cofactors. In this study we describe how swine ANP32A, uniquely among the mammalian ANP32 proteins tested, supports activity of avian origin influenza virus polymerases, and avian influenza virus replication. We further show that after the swine-origin influenza virus emerged in humans and caused the 2009 pandemic it evolved polymerase gene mutations that enabled it to more efficiently use human ANP32 proteins. We map the enhanced pro-viral activity of swine ANP32A to a pair of amino acids, 106 and 156, in the leucine-rich repeat and central domains and show these mutations enhance binding to influenza virus trimeric polymerase. These findings help elucidate the molecular basis for the 'mixing vessel' trait of swine and further our understanding of the evolution and ecology of viruses in this host.Importance Avian influenza viruses can jump from wild birds and poultry into mammalian species such as humans or swine, but only continue to transmit if they accumulate mammalian adapting mutations. Pigs appear uniquely susceptible to both avian and human strains of influenza and are often described as virus 'mixing vessels'. In this study, we describe how a host factor responsible for regulating virus replication, ANP32A, is different between swine and humans. Swine ANP32A allows a greater range of influenza viruses, specifically those from birds, to replicate. It does this through binding the virus polymerase more tightly than the human version of the protein. This work helps to explain the unique properties of swine as 'mixing vessels'.

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• Journal article
  Kellam P, Barclay W, 2020,

  The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection

  , Journal of General Virology, Vol: 101, ISSN: 0022-1317

  SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

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• Journal article
  Staller E, Baillon L, Frise R, Peacock T, Sheppard C, Sancho-Shimizu V, Barclay Wet al., 2020,

  A rare variant in ANP32B impairs influenza virus replication in human cells

  , biorxiv

  Viruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the human Anp32A and Anp32B genes. We note that variant rs182096718 in Anp32B is found at a higher frequency than other variants in either gene. This SNV results in a D130A substitution in ANP32B, which is less able to support FluPol activity than wildtype ANP32B and binds FluPol with lower affinity. Interestingly, ANP32B-D130A exerts a dominant negative effect over wildtype ANP32B and interferes with the functionally redundant paralogue ANP32A. FluPol activity and virus replication are attenuated in CRISPR-edited cells expressing wildtype ANP32A and mutant ANP32B-D130A. We propose a model in which the D130A mutation impairs FluPol dimer formation, thus resulting in compromised replication. We suggest that both homozygous and heterozygous carriers of rs182096718 may have some genetic protection against influenza viruses.

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• Journal article
  Lee LYY, Zhou J, Frise R, Goldhill DH, Koszalka P, Mifsud EJ, Baba K, Noda T, Ando Y, Sato K, Yuki A-I, Shishido T, Uehara T, Wildum S, Zwanziger E, Collinson N, Kuhlbusch K, Clinch B, Hurt AC, Barclay WSet al., 2020,

  Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission

  , PLOS PATHOGENS, Vol: 16, ISSN: 1553-7366
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  • Citations: 21
• Journal article
  Arinaminpathy N, Riley S, Barclay W, Saad-Roy C, Grenfell Bet al., 2020,

  Population implications of the deployment of novel universal vaccines against epidemic and pandemic influenza

  , Journal of the Royal Society Interface, ISSN: 1742-5662
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