Quinacrine, an Old Drug with Potentially usefull in the Treatment for COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Pineda B
PROVIDER: S-EPMC8180551 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Currently, there is no specific antiviral treatment for COVID-19. However, drugs previously developed to treat other viral infections are being tested to verify if they might also be effective against SARS-CoV-2, the virus that causes COVID-19. Twenty years ago, the F.D.A. approved Lopinavir/ritonavir (LPV/r) to treat HIV infection. LPV and ritonavir were initially purposed to inhibit 3-chymotrypsin-like protease (3CLpro) of SARS-CoV and MERS-CoV and preliminary promising data on its efficacy for treating people infected with those viruses were available. Therefore, due to the high genetic similarities among those viruses and SARS-CoV-2, early during COVID-19 pandemic LPV/r was also proposed as one emergency treatment. We reviewed data from the literature about LPV/r treatment and SARS-CoV-2 infection, mainly focused on the efficacy and safety of this drugs for COVID-19 treatment. We can conclude that although up to date no clear benefit has been observed with the LPV/r treatment beyond standard care, its efficacy against SARS-COV-2 infection deserves further evaluations, particularly during the very early phase of the disease.
| S-EPMC7654234 | biostudies-literature
Project description: Not available
| S-EPMC8412866 | biostudies-literature
Project description:Purpose of Review:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is a pandemic causing havoc globally. Currently, there are no Food and Drug Administration (FDA)-approved drugs to treat COVID-19. In the absence of effective treatment, off-label drug use, in lieu of evidence from published randomized, double-blind, placebo-controlled clinical trials, is common in COVID-19. Although it is vital to treat affected patients with antiviral drugs, there is a knowledge gap regarding the use of anti-inflammatory drugs in these patients. Recent Findings:Colchicine trials to combat inflammation in COVID-19 patients have not received much attention. We await the results of ongoing colchicine randomized controlled trials in COVID-19, evaluating colchicine's efficacy in treating COVID-19. Summary:This review gives a spotlight on colchicine's anti-inflammatory and antiviral properties and why colchicine may help fight COVID-19. This review summarizes colchicine's mechanism of action via the tubulin-colchicine complex. Furthermore, it discussed how colchicine interferes with several inflammatory pathways, including inhibition of neutrophil chemotaxis, adhesion, and mobilization; disruption of superoxide production, inflammasome inhibition, and tumor necrosis factor reduction; and its possible antiviral properties. In addition, colchicine dosing and pharmacokinetics, as well as drug interactions and how they relate to ongoing, colchicine in COVID-19 clinical trials, are examined.
| S-EPMC7367785 | biostudies-literature
Project description:Quinacrine is a potent antiprion compound in cell culture models of prion disease but has failed to show efficacy in animal bioassays and human clinical trials. Previous studies demonstrated that quinacrine inefficiently penetrates the blood-brain barrier (BBB), which could contribute to its lack of efficacy in vivo. As quinacrine is known to be a substrate for P-glycoprotein multi-drug resistance (MDR) transporters, we circumvented its poor BBB permeability by utilizing MDR(0/0) mice that are deficient in mdr1a and mdr1b genes. Mice treated with 40 mg/kg/day of quinacrine accumulated up to 100 microM of quinacrine in their brains without acute toxicity. PrP(Sc) levels in the brains of prion-inoculated MDR(0/0) mice diminished upon the initiation of quinacrine treatment. However, this reduction was transient and PrP(Sc) levels recovered despite the continuous administration of quinacrine. Treatment with quinacrine did not prolong the survival times of prion-inoculated, wild-type or MDR(0/0) mice compared to untreated mice. A similar phenomenon was observed in cultured differentiated prion-infected neuroblastoma cells: PrP(Sc) levels initially decreased after quinacrine treatment then rapidly recovered after 3 d of continuous treatment. Biochemical characterization of PrP(Sc) that persisted in the brains of quinacrine-treated mice had a lower conformational stability and different immunoaffinities compared to that found in the brains of untreated controls. These physical properties were not maintained upon passage in MDR(0/0) mice. From these data, we propose that quinacrine eliminates a specific subset of PrP(Sc) conformers, resulting in the survival of drug-resistant prion conformations. Transient accumulation of this drug-resistant prion population provides a possible explanation for the lack of in vivo efficacy of quinacrine and other antiprion drugs.
| S-EPMC2777304 | biostudies-other
Project description:The widespread coronavirus SARS-CoV-2 has already infected over 4 million people worldwide, with a death toll over 280,000. Current treatment of COVID-19 patients relies mainly on antiviral drugs lopinavir/ritonavir, arbidol, and remdesivir, the anti-malarial drugs hydroxychloroquine and chloroquine, and traditional Chinese medicine. There are over 2,118 on-going clinical trials underway, but to date none of these drugs have consistently proven effective. Cathepsin L (CatL) is an endosomal cysteine protease. It mediates the cleavage of the S1 subunit of the coronavirus surface spike glycoprotein. This cleavage is necessary for coronavirus entry into human host cells, virus and host cell endosome membrane fusion, and viral RNA release for next round of replication. Here we summarize data regarding seven CatL-selective inhibitors that block coronavirus entry into cultured host cells and provide a mechanism to block SARS-CoV-2 infection in humans. Given the rapid growth of the SARS-CoV-2-positive population worldwide, ready-to-use CatL inhibitors should be explored as a treatment option. We identify ten US FDA-approved drugs that have CatL inhibitory activity. We provide evidence that supports the combined use of serine protease and CatL inhibitors as a possibly safer and more effective therapy than other available therapeutics to block coronavirus host cell entry and intracellular replication, without compromising the immune system.
| S-EPMC7255230 | biostudies-literature
Project description:The consequences of the SARS-CoV-2 pandemic have exceeded any forecast made. Today we know that the level of severity of the infection in its initial stages will correspond to the evolution and the presence of sequelae in the future. There are no specific treatments that have shown sufficient evidence to allow their recommendation, especially in the mild-moderate stages of the disease. The anti-Covid vaccination is showing clear benefits, both in the prevention of the disease and in its evolution, with the consequent improvement in the numbers of those affected by the pandemic. The use of different drugs used in other indications has been proposed as possible beneficial treatments for COVID-19 that, if used, will be prescribed individually taking into account the characteristics and situation of the patient, the evolutionary phase of the disease as well as well as the limitations of the lack of evidence in its administration.
| S-EPMC8316068 | biostudies-literature
Project description:Introduction: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated. Areas covered: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy. Expert opinion: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.
| S-EPMC7441793 | biostudies-literature
Project description: Not available
| S-EPMC7167223 | biostudies-literature
Project description:Teicoplanin is an antibiotic that has been actively used in medical practice since 1986 to treat serious Gram-positive bacterial infections. Due to its efficiency and low cytotoxicity, teicoplanin has also been used for patients with complications, including pediatric and immunocompromised patients. Although teicoplanin is accepted as an antibacterial drug, its action against RNA viruses, including SARS-CoV2, has been proven in vitro. Here, we provide a thorough overview of teicoplanin usage in medicine, based on the current literature. We summarize infection sites treated with teicoplanin, concentrations of the antibiotic in different organs, and side effects. Finally, we summarize all available data about the antiviral activity of teicoplanin. We believe that, due to the extensive experience of teicoplanin usage in clinical settings to treat bacterial infections and its demonstrated activity against SARS-CoV2, teicoplanin could become a drug of choice in the treatment of COVID-19 patients. Teicoplanin stops the replication of the virus and at the same time avoids the development of Gram-positive bacterial co-infections.
| S-EPMC8708781 | biostudies-literature
Project description: Not available
| S-EPMC9272856 | biostudies-literature