Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19?

Abstract

Background: The current outbreak of pandemic coronavirus disease 2019 (COVID-19) aggravates serious need for effective therapeutics. Over recent years, drug repurposing has been accomplished as an important opportunity in drug development as it shortens the time consumed for development, besides sparing the cost and the efforts exerted in the research and development process. Main body of the abstract: The FDA-approved antiparasitic drug, nitazoxanide (NTZ), has been found to have antiviral activity against different viral infections such as coronaviruses, influenza, hepatitis C virus (HCV), hepatitis B virus (HBV), and other viruses signifying its potential as a broad spectrum antiviral drug. Moreover, it has been recently reported that NTZ exhibited in vitro inhibition of SARS-CoV-2 at a small micromolar concentration. Additionally, NTZ suppresses the production of cytokines emphasizing its potential to manage COVID-19-induced cytokine storm. Furthermore, the reported efficacy of NTZ to bronchodilate the extremely contracted airways can be beneficial in alleviating COVID-19-associated symptoms. Short conclusion: All these findings, along with the high safety record of the drug, have gained our interest to urge conductance of clinical trials to assess the potential benefits of using it in COVID-19 patients. Thus, in this summarized article, we review the antiviral activities of NTZ and highlight its promising therapeutic actions that make the drug worth clinical trials.

FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2

“…This approach offers the advantage of minimizing the required time, cost, and efforts for drug discovery process and safety evaluation. Furthermore, it reduces the risk of the drugs to fail, particularly due to safety issues since the majority of drugs are repositioned after verifying their safety in preclinical and clinical studies [9,10]. At the same time, drug repositioning demands an extensive study concerning the drug profile and new targeted disease mechanisms.…”

“…To rapidly define potential therapeutic options against SARS-CoV-2, testing existing Food and Drug Administration (FDA)-licensed drugs for efficacy against novel viral pathogens represents a practical approach for anti-CoV screening. This could expedite the recommendation and/or implementation of those FDA-approved drugs with effective anti-COVID-19 activity in the treatment protocol [9,10].…”

Hydroxychloroquine, nitazoxanide and ivermectin have similar effects in early COVID-19: a head-to-head comparison of the Pre-AndroCoV Trial.

“…Nitazoxanide demonstrated strong broad antiviral in vitro and in vivo activity (38,45,46), with clinical evidence of consistent antiviral activity in humans for a wide variety of virus families (46), with o cial indication for gastrointestinal viruses. Speci c anti-SARS-CoV-2 activity in vitro and in vivo has also been extensively demonstrated (46)(47)(48), and its plausibility as a promising therapy for COVID-19 found the strongest evidence between the three drugs, particularly when combined with azithromycin (48). Despite slightly less tolerable in terms of symptoms compared to hydroxychloroquine and ivermectin, intolerance rates are low.…”

COVID-19: the epidemiology and treatment

“…Given that SARS-CoV-2 does not encode any neuraminidase protein, neuraminidase inhibitors such as oseltamivir, zanamivir or lamivir are not thought to be effective for treating patients with COVID-19 . However, some studies have found that drugs including arbidol (Zhu et al, 2020), fusion peptide (EK1) (Xia et al, 2019), ganciclovir (Lai et al, 2020), Abelson (Abl) kinase inhibitor (imatinib) (Bernal-Bello et al, 2020), metronidazole (Gharebaghi et al, 2020), antiprotozoal drugs (nitazoxanide and ivermectin) (Mahmoud et al, 2020;Peña-Silva et al, 2020), and 3CL(Pro) inhibitors (Rathnayake et al, 2020) are efficacious when used to prevent SARS-CoV-2 infections in vitro. However, their safety and efficacy in preventing COVID-19 in humans remains to be determined.…”