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

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 proteins1–3. 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.