Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2
BackgroundAlthough tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previou...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1273982/full |
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| author | Shaibu Oricha Bello Shaibu Oricha Bello Shaibu Oricha Bello Mustapha Umar Imam Mustapha Umar Imam Muhammad Bashir Bello Muhammad Bashir Bello Abdulmajeed Yunusa Abdulmajeed Yunusa Adamu Ahmed Adamu Adamu Ahmed Adamu Abdulmalik Shuaibu Abdulmalik Shuaibu Ehimario Uche Igumbor Ehimario Uche Igumbor Zaiyad Garba Habib Zaiyad Garba Habib Mustapha Ayodele Popoola Chinwe Lucia Ochu Chinwe Lucia Ochu Aishatu Yahaya Bello Yusuf Yahaya Deeni Yusuf Yahaya Deeni Yusuf Yahaya Deeni Ifeoma Okoye |
| author_facet | Shaibu Oricha Bello Shaibu Oricha Bello Shaibu Oricha Bello Mustapha Umar Imam Mustapha Umar Imam Muhammad Bashir Bello Muhammad Bashir Bello Abdulmajeed Yunusa Abdulmajeed Yunusa Adamu Ahmed Adamu Adamu Ahmed Adamu Abdulmalik Shuaibu Abdulmalik Shuaibu Ehimario Uche Igumbor Ehimario Uche Igumbor Zaiyad Garba Habib Zaiyad Garba Habib Mustapha Ayodele Popoola Chinwe Lucia Ochu Chinwe Lucia Ochu Aishatu Yahaya Bello Yusuf Yahaya Deeni Yusuf Yahaya Deeni Yusuf Yahaya Deeni Ifeoma Okoye |
| author_sort | Shaibu Oricha Bello |
| collection | DOAJ |
| description | BackgroundAlthough tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells.AimThis study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (MPRO) enzymes.MethodsNeutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte® 520 SARS-CoV-2 papain-like protease and SensoLyte® 520 SARS-CoV-2 MPRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes.ResultsErythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC50) values 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 inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (MPRO) with IC50 values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively.ConclusionThe IC50 for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, 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. |
| first_indexed | 2024-03-09T14:45:35Z |
| format | Article |
| id | doaj.art-a5076e5ecdf6440c967b8e607afb01df |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-09T14:45:35Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-a5076e5ecdf6440c967b8e607afb01df2023-11-27T06:56:40ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-11-011310.3389/fcimb.2023.12739821273982Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2Shaibu Oricha Bello0Shaibu Oricha Bello1Shaibu Oricha Bello2Mustapha Umar Imam3Mustapha Umar Imam4Muhammad Bashir Bello5Muhammad Bashir Bello6Abdulmajeed Yunusa7Abdulmajeed Yunusa8Adamu Ahmed Adamu9Adamu Ahmed Adamu10Abdulmalik Shuaibu11Abdulmalik Shuaibu12Ehimario Uche Igumbor13Ehimario Uche Igumbor14Zaiyad Garba Habib15Zaiyad Garba Habib16Mustapha Ayodele Popoola17Chinwe Lucia Ochu18Chinwe Lucia Ochu19Aishatu Yahaya Bello20Yusuf Yahaya Deeni21Yusuf Yahaya Deeni22Yusuf Yahaya Deeni23Ifeoma Okoye24Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaNigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Lagos, NigeriaCentre for Advanced Medical Research and Training, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaCentre for Advanced Medical Research and Training, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaDepartment of Medical Biochemistry, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaCentre for Advanced Medical Research and Training, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaDepartment of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, NigeriaDepartment of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaCentre for Advanced Medical Research and Training, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaDepartment of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaCentre for Advanced Medical Research and Training, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaCentre for Advanced Medical Research and Training, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaDepartment of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, NigeriaNigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Lagos, NigeriaSchool of Public Health, University of the Western Cape, Cape Town, South AfricaNigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Lagos, NigeriaDepartment of Medicine, University of Abuja Teaching Hospital, Abuja, NigeriaNigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Lagos, NigeriaNigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Lagos, NigeriaNigerian Centre for Disease Control and Prevention, Abuja, NigeriaDepartment of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, NigeriaNigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Lagos, Nigeria0Department of Microbiology and Biotechnology, Federal University of Dutse, Dutse, Nigeria1Centre for Environmental and Public Health Research and Development, Kano, Nigeria2University of Nigeria Centre for Clinical Trials, University of Nigeria Teaching Hospital, Enugu, NigeriaBackgroundAlthough tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells.AimThis study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (MPRO) enzymes.MethodsNeutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte® 520 SARS-CoV-2 papain-like protease and SensoLyte® 520 SARS-CoV-2 MPRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes.ResultsErythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC50) values 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 inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (MPRO) with IC50 values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively.ConclusionThe IC50 for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, 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.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1273982/fullerythromycinretapamulinpyridoxinefolic acidivermectinSARS-CoV-2 |
| spellingShingle | Shaibu Oricha Bello Shaibu Oricha Bello Shaibu Oricha Bello Mustapha Umar Imam Mustapha Umar Imam Muhammad Bashir Bello Muhammad Bashir Bello Abdulmajeed Yunusa Abdulmajeed Yunusa Adamu Ahmed Adamu Adamu Ahmed Adamu Abdulmalik Shuaibu Abdulmalik Shuaibu Ehimario Uche Igumbor Ehimario Uche Igumbor Zaiyad Garba Habib Zaiyad Garba Habib Mustapha Ayodele Popoola Chinwe Lucia Ochu Chinwe Lucia Ochu Aishatu Yahaya Bello Yusuf Yahaya Deeni Yusuf Yahaya Deeni Yusuf Yahaya Deeni Ifeoma Okoye Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2 Frontiers in Cellular and Infection Microbiology erythromycin retapamulin pyridoxine folic acid ivermectin SARS-CoV-2 |
| title | Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2 |
| title_full | Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2 |
| title_fullStr | Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2 |
| title_full_unstemmed | Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2 |
| title_short | Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2 |
| title_sort | erythromycin retapamulin pyridoxine folic acid and ivermectin inhibit cytopathic effect papain like protease and mpro enzymes of sars cov 2 |
| topic | erythromycin retapamulin pyridoxine folic acid ivermectin SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1273982/full |
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