Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2

被引：1

作者：

Bello, Shaibu Oricha ^{[1
,2
,3
]}

Imam, Mustapha Umar ^{[3
,4
]}

Bello, Muhammad Bashir ^{[3
,5
]}

Yunusa, Abdulmajeed ^{[1
,3
]}

Adamu, Adamu Ahmed ^{[1
,3
]}

Shuaibu, Abdulmalik ^{[3
,5
]}

Igumbor, Ehimario Uche ^{[2
,6
]}

Habib, Zaiyad Garba ^{[2
,7
]}

Popoola, Mustapha Ayodele ^{[2
]}

Ochu, Chinwe Lucia ^{[2
,8
]}

Bello, Aishatu Yahaya ^{[9
]}

Deeni, Yusuf Yahaya ^{[2
,10
,11
]}

Okoye, Ifeoma ^{[12
]}

机构：

[1] Usmanu Danfodiyo Univ, Coll Hlth Sci, Fac Basic Clin Sci, Dept Pharmacol & Therapeut, Sokoto, Nigeria

[2] Nigerian Inst Med Res Inst, Nigerian COVID 19 Res Coalit, Abuja, Nigeria

[3] Usmanu Danfodiyo Univ, Coll Hlth Sci, Ctr Adv Med Res & Training, Sokoto, Nigeria

[4] Usmanu Danfodiyo Univ, Coll Hlth Sci, Dept Med Biochem, Sokoto, Nigeria

[5] Usmanu Danfodiyo Univ, Fac Vet Med, Dept Vet Microbiol, Sokoto, Nigeria

[6] Univ Western Cape, Sch Publ Hlth, Cape Town, South Africa

[7] Univ Abuja, Teaching Hosp, Dept Med, Abuja, Nigeria

[8] Nigerian Ctr Dis Control & Prevent, Abuja, Nigeria

[9] Usmanu Danfodiyo Univ, Fac Pharmaceut Sci, Dept Clin Pharm & Pharm Practice, Sokoto, Nigeria

[10] Fed Univ Dutse, Dept Microbiol & Biotechnol, Dutse, Nigeria

[11] Ctr Environm & Publ Hlth Res & Dev, Kano, Nigeria

[12] Univ Nigeria, Teaching Hosp, Ctr Clin Trials, Enugu, Nigeria

来源：

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY | 2023年 / 13卷

关键词：

erythromycin; retapamulin; pyridoxine; folic acid; ivermectin; SARS-CoV-2; COVID-19;

D O I：

10.3389/fcimb.2023.1273982

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Although 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.Aim: This 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 (M-PRO) enzymes.Methods: Neutral 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 (R) 520 SARS-CoV-2 papain-like protease and SensoLyte (R) 520 SARS-CoV-2 M-PRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes.Results: Erythromycin, 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 mu M, 4.23 mu M, 9.29 mu M, 3.19 mu M, and 84.31 mu M, respectively. Furthermore, erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 mu M, 0.88 mu M, 1.14 mu M, 1.07 mu M, and 1.51 mu M, respectively, and inhibited the main protease (M-PRO) with IC50 values of 1.35 mu M, 1.25 mu M, 7.36 mu M, 1.15 mu M, and 2.44 mu M, respectively.Conclusion: The 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.

引用

页数：9

共 45 条

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