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Effectiveness and safety of 7-day high-dose primaquine and single-dose tafenoquine versus 14-day low-dose primaquine in patients with Plasmodium vivax malaria (EFFORT): a multicentre, open-label, randomised, controlled, superiority trial.

BACKGROUND: Shorter courses of primaquine and single-dose tafenoquine have potential to improve the prevention of recurrent Plasmodium vivax … 70% or greater were eligible for enrolment. Patients were treated with blood schizonticidal drugs (chloroquine in Ethiopia and Pakistan, dihydroartemisinin-piperaquine in Indonesia, and artesunate-pyronaridine in Cambodia) and randomly assigned (1:1:1) by an independent statistician using randomly permuted blocks of varying sizes to receive 7 days of unsuper …

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis.

BACKGROUND: Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a sys … was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with sev …

Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2.

The COVID-19 global pandemic is caused by SARS-CoV-2, and represents an urgent medical and social issue. Unfortunately, there is still not a single proven effective drug available, and therefore, current therapeutic guidelines recommend supportive care including oxygen administration and treatment with antibiotics. Recently, patients have been also treated with off-label therapies which comprise antiretrovirals, anti-inflammatory compounds, antiparasitic agents and plasma from convalescent patients, all with controversial results. The ubiquitin-proteasome system (UPS) is important for the main

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… As an RNA polymerase inhibitor, it has been shown, alone or in combination with chloroquine or interferon-β, to effectively block the replication of SARS-CoV-2 [ 39 , 40 , 41 ]. … Chloroquine can inhibit the pH-dependent phases of the replication of different viruses [ 44 ], with a powerful effect on the infection and spread of SARS-CoV [ 45 ]. Furthermore, chloroquine has immuno-modulatory effects, suppressing the production/release of TNF-α and IL-6. …

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

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… Chloroquine significantly decreased HCV-RNA in Hepatitis C in a quadruple-blind, randomized Phase IV study ( Peymani et al., 2016 ). … PINC trial: Preventing invasive breast neoplasia with chloroquine . Cancer Res. 77 , Abstract nr CT140. 10.1158/1538-7445.am2017-ct140 Fang E. F. Scheibye-Knudsen M. Brace L. E. Kassahun H. Sengupta T. Nilsen H. ( 2014 ). …

Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis.

BACKGROUND: Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is lim … was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We exclu …

Phytochemical synergy in artemisia annua herbal tea against malaria: a systematic review of its efficacy and safety in the context of emerging Pfkelch13 resistance.

BACKGROUND: Emerging Plasmodium falciparum resistance to artemisinin derivatives, mediated principally by mutations in the Pfkelch13 propell … nt IC50 values were 3-5 × lower than those of equivalent-concentration purified artemisinin on 3D7, chloroquine-resistant, and multidrug-resistant strains. In Pfkelch13-mutant rodent P. falciparum lines, stable resistance to whole-plant therapy emerged three times more slowly than to equivalent-dose purified dihydroartemisinin. Clinically, retained randomised …

Tegument protein UL16 of herpes simplex virus 1 suppresses the innate immune response by downregulating MAVS abundance via mitophagy.

Herpes simplex virus 1 (HSV-1) is a globally prevalent pathogen that poses a significant health threat due to its lifelong latency. This per … : cyclic GMP-AMP synthase; co-IP: co-immunoprecipitation; COX8: cytochrome c oxidase subunit 8; CQ: chloroquine; CRISPR: clustered regulatory interspaced short palindromic repeat; CTD: C-terminal domain; Ctrl: control; CXCL10: C-X-C motif chemokine ligand 10; DAPI: 4,'6-diamidino-2-phenylindole; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxi …

[Clinical efficacy and safety of different antiviral regimens in patients with coronavirus disease 2019].

OBJECTIVE: To investigate the clinical efficacy and short-term and long-term adverse reactions for different antiviral regiments for coronav … nconventional antiviral group was given α-interferon combined with LPV/R and Abidor or Ribavirin or Chloroquine. The patients were divided into mild (13 cases), ordinary (45 cases), severe (14 cases) and critical (1 case) types. The clinical data, length of hospital stay, the first 2019 novel coronavirus (2019-nCoV) nucleic acid negative recovery time, cost o …

COVID-19 Presented With Deep Vein Thrombosis: An Unusual Presenting.

On December 31, 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. The pneumonia was caused by a virus called SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2), which was later named coronavirus infectious disease 2019 (COVID-19). The symptoms most commonly reported by patients affected by COVID-19 include fever, dry cough, and shortness of breath. In this report, we present a case of a 57-year-old woman who presented to the clinic's infectious department with swelling, pain, warmth, and

Perinatal use and discontinuation of disease-modifying anti-rheumatic drugs and biologics in women with rheumatoid arthritis: a cohort study.

OBJECTIVES: To characterize the utilization and discontinuation of medications before, during and after pregnancy among women with RA. METHODS: We used population-based administrative data to identify women with RA who had a singleton pregnancy ending in delivery between 1 January 2002 and 31 December 2012. We assessed the utilization of RA medications, namely, conventional synthetic DMARDs, biologics, glucocorticosteroids and NSAIDs, across six windows spanning 24 and 12 months before the start of pregnancy, each trimester of pregnancy and 12 months post-pregnancy. We defined medication disc

Possible treatment and strategies for COVID-19: review and assessment.

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly incr … pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can …

COVID-19: A 2020 update

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… during the SARS epidemic suggested that the anti-malarial drugs chloroquine and hydroxychloroquine (HCQ) may be clinically beneficial. … Anti-malarial | Antiviral | Anti-parasitic | Immunomodulatory Chloroquine | Remdesivir | Nitazoxanide | Tocilizumab Hydroxy | | | chloroquine | Ribavirin | Ivermectin | Convalescent plasma | Ritonavir/lopinavir | | BCG vaccine Antiviral agents Remdesivir is a nucleotide analog antiviral medication …

Tackling the cytokine storm in COVID-19, challenges and hopes.

The outbreak of Coronavirus disease 2019 (COVID-19) is the current world health concern, presenting a public health dilemma with ascending morbidity and mortality rates exceeding any previous viral spread, without a standard effective treatment yet. SARS-CoV-2 infection is distinguished with multiple epidemiological and pathological features, one of them being the elevated levels of cytokine release, which in turn trigger an aberrant uncontrolled response known as "cytokine storm". This phenomenon contributes to severe acute respiratory distress syndrome (ARDS), leading to pneumonia and respir

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… Chloroquine/hydroxychloroquine Chloroquine (CQ) has long been used for prophylaxis and treatment of malaria [ 86 ]. Hydroxychloroquine (HCQ) sulfate salt is more soluble and much less toxic metabolite of CQ. … Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J. 2005;2:69. doi: 10.1186/1743-422X-2-69. 96. Wang M., Cao R., Zhang L., et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. …

Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 M

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… | 1 Darunavir/ritonavir+oseltamivir+chloroquine | 1 Favipiravir+chloroquine | 2 Hydroxychloroquine+lopinavir or atazanavir/ritonavir | 1 Hydroxychloroquine+oseltamivir+lopinavir+interferon | 1 Lopinavir/ritonavir+chloroquine | 1 Lopinavir/ritonavir+hydroxychloroquine | 1 Oseltamivir+chloroquine | 1 … Solidarity , announced by the WHO on 20 March 2020, is a multicentre, adaptive, randomised, open-label, five-arm trial testing remdesivir, chloroquine/hydroxychloroquine, ritonavir/lopinavir and ritonavir/lopinavir with interferon-beta against standard of care in dozens of countries around the globe. …

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they

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… Antimalarial agents Chloroquine & hydroxychloroquine Chloroquine and Hydroxychloroquine are antimalarial drugs that inhibit lysosomes' vital functions by increasing pH, which results in blocking endosome-mediated entry ( Al-Bari, 2017 ). … Besides, another in vitro study was designed to compare the antiviral effects of Hydroxychloroquine and Chloroquine. The 50% cytotoxic concentration (CC50) values were evaluated as 273.20 and 249.50 μM for Chloroquine and Hydroxychloroquine, respectively. …

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immun…

Drug Repurposing of New Treatments for Neuroendocrine Tumors.

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metas

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… Chloroquine (CQ) and hydroxychloroquine (HCQ) exert anti-cancer effects through several key mechanisms. … Preclinical studies suggested that autophagy inhibition by chloroquine/hydroxychloroquine could be used for the treatment of pNETs, including the well-differentiated type [ 44 ]. …

The role of autophagy in cancer: from molecular mechanism to therapeutic window.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy a

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… Chloroquine and hydroxychloroquine Autophagy was directly suppressed by chloroquine (CQ) and hydroxychloroquine (HCQ), which have previously been used to prevent and cure malaria ( 369 ), by altering lysosomal pH, stopping autophagic breakdown, and increasing autophagosomal accumulation ( 370 , 371 … In Table 1 , the clinical trials investigating the effects of chloroquine and hydroxychloroquine on various cancers are presented. Table 1 Clinical trials with Chloroquine (CQ) and hydroxychloroquine (HCQ) for Cancer treatment. …

Repurposing Drugs in Oncology (ReDO)-mebendazole as an anti-cancer agent.

Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer

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… Chloroquine/Hydroxychloroquine : The anti-malarial drugs chloroquine and hydroxychloroquine are under active investigation in a range of clinical trials for cancer in combination with radiotherapy and/or alongside existing chemotherapy regimens. … There are a number of clinical trials combining the autophagy inhibitor chloroquine with a range of chemotherapeutic drugs, including microtubule disrupters, in different cancers. …

Potential drug development and therapeutic approaches for clinical intervention in COVID-19.

While the vaccination is now available to many countries and will slowly dissipate to others, effective therapeutics for COVID-19 is still illusive. The SARS-CoV-2 pandemic has posed an unprecedented challenge to researchers, scientists, and clinicians and affected the wellbeing of millions of people worldwide. Since the beginning of the pandemic, a multitude of existing anti-viral, antibiotic, antimalarial, and anticancer drugs have been tested, and some have shown potency in the treatment and management of COVID-19, albeit others failed to leave any positive impact and a few also became cont

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… Chloroquine phosphate inhibits ACE2 phosphorylation, whereas hydroxychloroquine promotes endosomal pH and is implicated in the virus entry [202] , [203] . Early reports showed that Chloroquine phosphate inhibits SARS-CoV infection with a high in vitro activity [202] , [204] , [205] . … Chloroquine Wang et al. evaluated the anti-viral efficiency of some well-known broad-spectrum anti-viral drugs against a clinical isolate of SARS-CoV-2 in vitro , where Chloroquine ( Fig. 7 ) potently blocked virus infection at low-micromolar concentration with an EC 50 value of 1.13 µM and showed high …