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    Antiviral activity of glucose-derived reactive metabolite, methylglyoxal against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

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    jemtac.2022.qhc.8.pdf (211.1Kb)
    Date
    2022
    Author
    AlKhatib, Hebah A M
    ElBashir, Israa
    Yassine, Hadi M.
    Thornalley, Paul J
    Rabbani, Naila
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    Abstract
    Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in a global health emergency. With incomplete vaccination and incomplete protection of the vaccinated population, there remains an urgent need to develop drugs to treat COVID-19. Our previou in silico analysis suggested vulnerability of SARS-CoV-2 to inactivation by the endogenous reactive metabolite, methylglyoxal (MG), by modification of arginine residues in the functional domains of viral spike and nucleocapsid proteins 1–3 . In this study, the antiviral activity of MG against wild-type SARS-CoV-2 using in vitro assays was evaluated. Methods: Wild-type SARS-CoV-2 with titers of multiplicities of infection (MOI) 0.8, 0.2, 0.02, and 0.01 were incubated with 2-fold serial dilutions of MG (7.8 μM to 500 μM) in infection medium for six hour. MG-treated and untreated control SARS-CoV-2 were incubated with confluent cultures of Vero cells in vitro for one hour, cultures were washed and then incubated in a fresh infection medium at 37°C for 4 - 5 days until 70% of virus–infected cells displayed cytopathic effect (CPE). The antiviral activity of MG was judged by assessing virus replication using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and median tissue culture infectious dose (TCID50) assays. Results: MG inhibited virus replication as measured by PCR and CPE of SARS-CoV-2 in vitro, with TCID50 increasing with increasing MOI. MG was most potent at MOI 0.02 and 0.01 where EC50 of MG was 49.6 ± 4.7 μM and 28.5 ± 1.3μM; respectively. Similar findings were also found for a shorter incubation period (3 hours) of MG and virus. Conclusion: MG has inhibitory activity against wild-type SARS-CoV-2 for virus exposure in the cell-free systems at low MOI. However, the antiviral activity of MG against other SARS-CoV-2 variants including alpha- and beta-variants is being investigated. Drugs increasing cellular concentration of MG to viricidal levels may have anti-COVID-19 activity.
    URI
    https://doi.org/10.5339/jemtac.2022.qhc.8
    DOI/handle
    http://hdl.handle.net/10576/28947
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    • Biomedical Research Center Research [‎808‎ items ]
    • COVID-19 Research [‎849‎ items ]
    • Medicine Research [‎1819‎ items ]

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