Erythromycin, Retapamulin, Pyridoxine, Folic acid, and Ivermectin dose-dependently inhibit cytopathic effect, Papain-like Protease, and MPRO of SARS-CoV-2

Bello, S. O.; Imam, M. U.; Bello, M. B.; Yunusa, A.; Adamu, A. A.; Shuaibu, A.; Igumbor, E. U.; Habib, Z. G.; Popoola, M. A.; Ochu, C. L.; Bello, A. Y.; Deeni, Y. Y.; Okoye, I.

doi:10.1101/2022.12.28.522082

bioRxiv · 10.1101/2022.12.28.522082

Erythromycin, Retapamulin, Pyridoxine, Folic acid, and Ivermectin dose-dependently inhibit cytopathic effect, Papain-like Protease, and MPRO of SARS-CoV-2

Bello, S. O.·Imam, M. U.·Bello, M. B.·Yunusa, A.·Adamu, A. A.·Shuaibu, A.·Igumbor, E. U.·Habib, Z. G.·Popoola, M. A.·Ochu, C. L.·Bello, A. Y.·Deeni, Y. Y.·Okoye, I.

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Abstract

We 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 M, 4.23 M, 9.29 M, 3.19 M and 84.31 M respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50 of 0.94 M, 0.88 M, 1.14 M, 1.07 M, 1.51 M respectively and the main protease(MPRO) with IC50 of 1.35 M, 1.25 M, 7.36 M, 1.15 M and 2.44 M respectively. The IC50 for 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.

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Bello, S. O., Imam, M. U., Bello, M. B., Yunusa, A., Adamu, A. A., Shuaibu, A., Igumbor, E. U., Habib, Z. G., Popoola, M. A., Ochu, C. L., Bello, A. Y., Deeni, Y. Y., Okoye, I.. 2022-12-29. Erythromycin, Retapamulin, Pyridoxine, Folic acid, and Ivermectin dose-dependently inhibit cytopathic effect, Papain-like Protease, and MPRO of SARS-CoV-2. https://doi.org/10.1101/2022.12.28.522082

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