Browsing by Author "Cooper, Gemma"

Now showing 1 - 4 of 4
  • No Thumbnail Available
    ItemOpen Access
    Hydroxy-xanthones as promising antiviral agents: synthesis and biological evaluation against human coronavirus OC43
    (Elsevier, 2023-02-28) Dean, Bethanie; Cooper, Gemma; Shivkumar, Maitreyi; Snape, Timothy J.
    A number of synthetic hydroxy-xanthones related to isolates from the plant genus Swertia (family Gentianaceae) were prepared and their antiviral activity assessed against human coronavirus OC43. Overall, the results of the initial screening of the test compounds in BHK-21 cell lines show promising biological activity, with a significant reduction in viral infectivity (p≤0.05). In general, the addition of functionality around the xanthone core increases the biological activity of the compounds compared to xanthone itself. More detailed studies are needed to determine mechanism of action, but favourable property predictions make them interesting lead compounds for further development as potential treatments for coronavirus infections.
  • Thumbnail Image
    ItemOpen Access
    Investigating the antiviral activity of bioactive Swertia chirayita compounds against coronaviruses.
    (2022-09-07) Cooper, Gemma; Dean, Bethanie; Snape, Timothy J.; Shivkumar, Maitreyi
    Aim: The emergence of three pandemic coronaviruses in the last two decades combined with numerous coronaviruses circulating in bats suggest that spillover of new coronaviruses into humans is likely in the future. The development of broad-spectrum antivirals is vital to allow rapid deployment to patients in the absence of a pan-coronavirus vaccine. This project aims to employ a model coronavirus system as an initial screening tool to identify novel natural product-derived antivirals. Methods: Antiviral activity of a panel of natural compounds and synthetic xanthones based on bioactive compounds from the medicinal plant Swertia chirayita were tested against a model seasonal human coronavirus (HCoV) OC43. Infected baby hamster kidney (BHK-21) cells were treated with compounds and impact on infectivity determined by quantifying viral titres. Alongside, cytotoxicity of the compounds was also determined. Results: Our initial screen identified six compounds that indicated antiviral activity, with synthetic xanthones showing a significant reduction in viral infectivity of HCoV-OC43 at non-cytotoxic concentrations. Preliminary experiments suggest that these inhibit the virus at early stages of the viral life cycle. Conclusions: We have identified bioactive compounds derived from Swertia chirayita, which show significant antiviral efficacy in a human coronavirus. Further work to evaluate their pan-coronavirus activity, as well as to understand the mechanism of action are on-going.
  • Thumbnail Image
    ItemOpen Access
    Investigating the antiviral activity of natural product derived compounds and synthetic xanthones against coronaviruses.
    (2023-07-24) Cooper, Gemma; Dean, Bethanie; Snape, Timothy J.; Shivkumar, Maitreyi
    In the last 20 years three pandemic coronaviruses have emerged, with many more coronaviruses circulating in animal reservoirs, future spillover into humans is likely. The development of novel pan-coronavirus antivirals is vital to target new emerging coronaviruses and enhance future pandemic preparedness. Here, we investigated the antiviral activity of a panel of natural product compounds derived from Swertia chirayita for their anti-coronavirus activities. A panel of compounds and synthetic xanthones based on Swerita bioactive compounds was assessed for antiviral activity against human coronavirus OC43 and 229E, and SARS-CoV-2 pseudoviruses. Infected cell lines were treated with the compounds, and impact on infectivity assessed by quantifying viral titres. Alongside, cytotoxicity of the compounds was determined. The initial screen identified six natural product compounds that display antiviral activity at non-cytotoxic concentrations. While the synthesised xanthones show a significant reduction in viral infectivity, the inhibition was not as potent as seen in the natural xanthone mangiferin. This suggests that the additional complexity of mangiferin and other naturally derived xanthones may contribute to their increased antiviral activities. Our preliminary data investigating the mechanism of action suggests that the hit compounds inhibit the virus at early stages in the viral lifecycle. The six compounds identified are being carried forward for further investigations. With mechanism of action studies and viral target determination currently ongoing, this work is a step towards identifying novel pan-coronavirus antivirals.
  • Thumbnail Image
    ItemOpen Access
    Investigating the antiviral activity of volatile compounds from Nigella sativa against coronaviruses.
    (2023-04-17) Cooper, Gemma; Khodeir, Hesham F.I.; Kamoona, Karrar; Alalaqi, Ahmed; Haris, P. I. (Parvez I.); Shivkumar, Maitreyi
    The recent emergence of three major coronaviruses and presence of coronaviruses circulating in bats suggests that spillover of new pandemic-potential coronaviruses into humans is likely in future. The development of pan-coronavirus antivirals will be crucial to combat this. Here, we investigated the antiviral activities of Nigella sativa (black cumin) oil extracts from various global locations against seasonal human coronaviruses OC43 and 229E, and SARS-CoV-2 pseudoviruses. Coronavirus-infected cells were directly treated with oil extracts and antiviral activity determined by quantifying viral titres. In diffusion assays, oils were incubated in microwell plates with virus in adjacent wells to investigate the effect of diffused volatile compounds. After incubation over a range of times, infectivity was determined. Our diffusion assay results indicate that volatile compounds present in Nigella sativa extracts show antiviral activities against coronaviruses, with no cytotoxic effect on cells. Significant inhibition of infection was observed after 12 hours incubation, with the most potent oils showing a ≥4 log10 reduction in OC43 infectivity at 24 hours. Interestingly, direct treatment of infected cells with oils showed limited antiviral efficacy, suggesting that the vapour phase may offer higher concentrations of the bioactive compounds without compromising cell viability. We also identified key volatile compounds present in the oil vapour phase; evaluation of the antiviral activity of these volatiles in isolation and in synergy are ongoing. Overall, this work provides a first step towards identifying novel pan-coronavirus antiviral compounds that can be formulated as sprays or inhalers for direct delivery to the site of infection.