Antiviral activity of glucose-derived reactive metabolite, methylglyoxal against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Author | AlKhatib, Hebah A M |
Author | ElBashir, Israa |
Author | Yassine, Hadi M. |
Author | Thornalley, Paul J |
Author | Rabbani, Naila |
Available date | 2022-03-24T05:33:56Z |
Publication Date | 2022 |
Publication Name | Journal of Emergency Medicine, Trauma and Acute Care |
Resource | qscience |
Citation | AlKhatib HAM, ElBashir I, Yassine HM, Thornalley PJ, Rabbani N. Antiviral activity of glucose-derived reactive metabolite, methylglyoxal against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Journal of Emergency Medicine, Trauma & Acute Care 2022:8 http://dx.doi.org/10.5339/jemtac.2022.qhc.8 |
ISSN | 1999-7086 |
ISSN | 1999-7094 |
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. |
Language | en |
Publisher | Hamad bin Khalifa University Press (HBKU Press) |
Subject | SARS-CoV-2 COVID-19 methylglyoxal antiviral |
Type | Article |
Issue Number | 1 |
Volume Number | 2022 |
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