Recent Developments in Therapies and Strategies Against COVID-19
Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga in The Covid-19 Pandemic, 2023
Nitazoxanide is a broad-spectrum antiviral and antiparasitic agent. It is used for the treatment of different helminthic, protozoal, and viral infections. Nitazoxanide is the prototype agent of the thiazolides, which is a group having synthetic nitrothiazolyl-salicylamide derivatives with antiviral and antiparasitic activity. Tizoxanide, an active metabolite of nitazoxanide also antiparasitic drug of the thiazolide class. Clinical trials of nitazoxanide against influenza has been done and shown inhibitory effect on a broad range of influenza virus subtypes. The drug is also effective against influenza viruses which develop some resistance to neuraminidase inhibitors like oseltamivir Nitazoxanide is also being investigated as a potential treatment for chronic hepatitis B, chronic hepatitis C, norovirus gastroenteritis and rotavirus.
Drug Repurposing and Novel Antiviral Drugs for COVID-19 Management
Debmalya Barh, Kenneth Lundstrom in COVID-19, 2022
Nitazoxanide, a small-molecule (nitrothiazolyl-salicylamide) antiprotozoal drug marketed as tablets (500 mg) and suspension (100 mg/5 ml), is mainly indicated in protozoa Cryptosporidium or Giardia diarrhea in adults and children. In in vitro studies, the molecule has demonstrated a broad spectrum of antiviral efficacy against respiratory syncytial virus (RSV), parainfluenza virus, coronavirus (CoV), rotavirus, norovirus, hepatitis B virus (HBV), hepatitis C virus (HCV), Dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), and human immunodeficiency virus (HIV). Few clinical trials have proved its role in gastroenteritis, hepatitis and influenza. A special quality is its ability to promote balance between pro-inflammatory and anti-inflammatory mediators in acute conditions and this is potentially helpful in management of hyper inflammatory cytokine storm in patients with COVID-19. Repurposing nitazoxanide against COVID-19 has been reported in many studies. Two phase III trials for prevention of COVID-19 in high-risk, elderly populations, and healthcare workers are ongoing [33, 34] Another multi-center, randomized, double-blind phase III study was initiated in August 2020 for the treatment of COVID-19 patients aged 12 years and older [35].
An Outbreak of Cryptosporidium sp. Associated with a Public Swimming Pool
Meera Chand, John Holton in Case Studies in Infection Control, 2018
Treatment options are limited. Rehydration with oral or intravenous fluids may be required. The aim of treatment in immunocompromised patients is improvement of symptoms, with complete clearance of the parasite unlikely unless the underlying immune deficiency can be corrected. In HIV-infected individuals, resolution of symptoms relies on restoration of immune status using highly active antiretroviral therapy (HAART). HAART improves the CD4 count and restores a degree of immunity. In addition, protease inhibitors seem to have some antiparasitic activity, an effect enhanced with paromomycin. In the US, nitazoxanide, a thiazole compound, is licensed for use and available by regular prescription for disease in immunocompetent patients >1 year old. It has been shown to decrease severity and duration of symptoms in this patient group. Parasite clearance has also been demonstrated. There is less conclusive evidence of the benefits of nitazoxanide in immunocompromised individuals. In the subgroup with the most advanced HIV disease, it has been shown not to be effective. Nitazoxanide is not licensed in the European Union but is available in the UK on a named-patient basis.
Host-directed therapies for malaria and tuberculosis: common infection strategies and repurposed drugs
Published in Expert Review of Anti-infective Therapy, 2022
Piyush Baindara, Sonali Agrawal, O. L. Franco
The most advanced example of drug repurposing is the case of the antiparasitic drug nitazoxanide, currently being repurposed for the treatment of influenza [189]. Nitazoxanide, a broad-spectrum antiparasitic and antiviral drug, is used in medicine for the treatment of various helminthic, protozoal, and viral infections [190–192]. Lam et al. 2012 reported that antiprotozoal drug nitazoxanide and its active metabolite tizoxanide strongly stimulate autophagy through inhibiting signaling by mTORC1. Nitazoxanide treatment was also found to inhibit both replicating and non-replicating forms of Mtb [193]. Furthermore, its low eukaryotic cytotoxicity, with no reports of resistance to Mtb mutant strains, makes this drug more promising. In malaria, co-administration of nitazoxanide with the intermittent preventive treatment of malaria in infants or children has been suggested [194].
Discovery of novel antischistosomal scaffolds from the open access Pandemic Response Box
Published in Expert Review of Anti-infective Therapy, 2022
Stefan Biendl, Cécile Häberli, Jennifer Keiser
Our screen identified nitazoxanide as a compound eliciting fast-acting antischistosomal activity with a sub-micromolar EC50 after 24 h of parasite drug exposure against adult worms. Since El-Taweel and coworkers already thoroughly evaluated the effects of nitazoxanide in S. mansoni infected mice, we excluded this compound from further evaluation. In their study, nitazoxanide showed worm burden reductions of ~45% and ~62% for the observational time points 2 and 4 weeks post-treatment, respectively, after oral administration of 100 mg/kg body weight for seven consecutive days [23]. We excluded two further compounds from in vivo activity studies because of expected toxicity at high oral doses. Firstly, the promiscuous mixed lineage kinase (MLK) inhibitor URMC-099 (MMV1580482) that is blood–brain barrier (BBB) penetrant and currently under investigation for the treatment of neuronal disorders [27] and, secondly, the bis-biguanide topical antiseptic alexidine (MMV39678,) [21].
Possible therapeutic agents for COVID-19: a comprehensive review
Published in Expert Review of Anti-infective Therapy, 2020
Khaled Mosaad Elhusseiny, Fatma Abd-Elshahed Abd-Elhay, Mohamed Gomaa Kamel
Nitazoxanide is another potential therapeutic for COVID-19. It has shown a broad spectrum of anti-parasitic and antiviral activity acting against rotavirus, norovirus, chronic hepatitis B, influenza, respiratory syncytial virus, canine CoVs through distinctive mechanisms [838485–87]. It was found to overexpress interferon regulatory factor-1 that inhibited the replication of human norovirus [87]. Moreover, it was found to be active against MERS-CoV, murine, and bovine CoVs through inhibition of the viral N protein expression [86]. Additionally, it suppresses the production of inflammatory cytokines, including IL-2, IL6, and IL-10 [88]. Besides, the in vitro efficacy of nitazoxanide against SARS-CoV-2 was reported [16,26]. The most commonly reported side effects of nitazoxanide are mild, including headache, skin rash, fever, vomiting, and abdominal pain [89,90]. To date, 11 registered trials are trying to investigate its safety and efficacy in COVID-19 patients either alone or in combination with ivermectin or hydroxychloroquine with their findings yet to be revealed [91].
Related Knowledge Centers
- Cryptosporidium Parvum
- Drug Repositioning
- Immunocompetence
- Virus
- Influenza
- Antiparasitic
- Broad-Spectrum Antiviral Drug
- Parasitic Worm
- Giardia Duodenalis
- Drug Class