Pyridoxine for COVID-19

Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods. The drugs were screened at doses that are known to be achievable in humans. Furthermore, inhibition of viral induced cytopathic effect (CPE) was used as the laboratory surrogate to predict efficacy. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms.

AbstractWe previously showed that Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin inhibit SARS-COV-2 induced cytopathic effect (CPE) in Vero cells. In this study and using validated quantitative neutral red assay, we show that the inhibition of CPE is concentration dependent with Inhibitory Concentration-50(IC50) of 3.27 μM, 4.23 μM, 9.29 μM, 3.19 μM and 84.31 μM respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50of 0.94 μM, 0.88 μM, 1.14 μM, 1.07 μM, 1.51 μM respectively and the main protease(MPRO) with IC50of 1.35 μM, 1.25 μM, 7.36 μM, 1.15 μM and 2.44 μM respectively. The IC50for all the drugs, except ivermectin, are at the clinically achievable plasma concentration in human, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by Ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.