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1.
Front Public Health ; 10: 788972, 2022.
Article in English | MEDLINE | ID: covidwho-1798916

ABSTRACT

The COVID-19 pandemic has been characterized by a lack of clear evidence to guide healthcare professionals, the public and policymakers. The resulting uncertainty, coupled with changing guidelines as additional evidence became available, added to the stress and anxiety reported by decision-makers. Research results are key to providing evidence to guide healthcare decisions. Important questions have arisen about whether various interventions are safe and effective. The evidence found guides those making treatment decisions, and influences those selecting interventions for further evaluation in research studies. As the COVID-19 pandemic intensified, the effectiveness and safety of many pharmaceuticals was queried. Ivermectin will be used to explore the ethics of how healthcare evidence must be critically appraised, even, or especially, during a pandemic. This drug is alleged to be effective in treating COVID-19, with various studies and systematic reviews finding supportive evidence. Some of these have now been linked to concerns about fraud or poor research reporting. This article will focus on the scientific literature and how apparently fraudulent studies were published and influenced treatment decisions, on-going research and public health guidelines. Research evidence is critical during emergencies like pandemics, but urgency should not overtake ethical responsibilities to critically appraise (or evaluate) studies as they become available. These responsibilities apply in various ways to editors, peer-reviewers, news media reporters, and those making treatment decisions, including clinicians, policymakers and the general public. While research article authors have the primary ethical responsibility to reject fraudulent or inaccurate claims, the readers of health research must carefully evaluate all publications. To detect and reject fraudulent healthcare claims, readers need critical appraisal skills that match their level of engagement with those articles. The core principles of critical appraisal will be described in the article, and how they can be adapted for different types of readers. Exemplar tools that develop critical appraisal skills will be noted, with reviews of ivermectin's efficacy explored as examples. As stakeholders in healthcare evidence are increasingly able to identify well-conducted and ethical research they will simultaneously be able to spot and reject fraudulent reports and prevent them from influencing healthcare decisions.


Subject(s)
COVID-19 , Ivermectin , COVID-19/drug therapy , Decision Making , Delivery of Health Care , Humans , Ivermectin/therapeutic use , Pandemics
2.
JAMA Netw Open ; 5(3): e223079, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1750275

ABSTRACT

Importance: A widely cited meta-analysis of randomized clinical trials has claimed ivermectin as an effective treatment for prevention of mortality in COVID-19. However, an unrecognized interaction variable with the relative risk (RR) of mortality may substantially change the appropriate interpretation of this analysis. Objective: To evaluate the association between regional prevalence of strongyloidiasis and ivermectin trial results for the outcome of mortality by testing the hypothesis that strongyloidiasis prevalence interacts with the RR of mortality. Data Sources: Original meta-analysis as well as a manual review of all references in a dedicated ivermectin trial database (c19ivermectin) from January 1, 2019, to November 6, 2021. Study Selection: Randomized clinical trials using ivermectin as a treatment for COVID-19 and reporting the outcome of mortality. Studies were excluded in the event of publications revealing suspected trial fraud and/or randomization failure. Data Extraction and Synthesis: Study characteristics and RR estimates were extracted from each source. Estimates were pooled using random-effects meta-analysis. Differences by strongyloidiasis prevalence were estimated using subgroup meta-analysis and meta-regression. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Main Outcomes and Measures: Relative risk of mortality in ivermectin trials in regions of high vs low strongyloidiasis prevalence and correlation coefficient of meta-regression analysis between RR of mortality and regional prevalence of strongyloidiasis. Results: A total of 12 trials comprising 3901 patients were included in the analysis. Four trials (33%) took place in regions of high strongyloidiasis prevalence and 8 (67%) trials took place in regions of low strongyloidiasis prevalence. Ivermectin trials that took place in areas of low regional strongyloidiasis prevalence were not associated with a statistically significant decreased risk of mortality (RR, 0.84 [95% CI, 0.60-1.18]; P = .31). By contrast, ivermectin trials that took place in areas of high regional strongyloidiasis prevalence were associated with a significantly decreased risk of mortality (RR, 0.25 [95% CI, 0.09-0.70]; P = .008). Testing for subgroup differences revealed a significant difference between the results of groups with low and high strongyloidiasis prevalence (χ21 = 4.79; P = .03). The estimate for τ2 (the variance of the study effect sizes) was 0 (95% CI, 0.0000-0.2786), and the estimate for I2 (percentage of variability that is explained by between-study heterogeneity) was 0 (95% CI, 0-43.7%). The meta-regression analysis revealed an RR decrease of 38.83% (95% CI, 0.87%-62.25%) for each 5% increase in strongyloidiasis prevalence. Conclusions and Relevance: In this meta-analysis of 12 trials including 3901 patients, strongyloidiasis prevalence was found to interact with the RR of mortality for ivermectin as a treatment for COVID-19. No evidence was found to suggest ivermectin has any role in preventing mortality among patients with COVID-19 in regions where strongyloidiasis was not endemic.


Subject(s)
Antiparasitic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Endemic Diseases , Ivermectin/therapeutic use , Strongyloidiasis/epidemiology , Humans , Prevalence , Randomized Controlled Trials as Topic , Risk , Strongyloidiasis/drug therapy
4.
Clin Toxicol (Phila) ; 60(5): 571-575, 2022 May.
Article in English | MEDLINE | ID: covidwho-1711284

ABSTRACT

Introduction: Avermectins are common antiparasitic drugs, derived from Streptomyces bacteria that exhibit activity against arthropods and nematodes. Ivermectin, an avermectin derivative, is used as a treatment for parasitic infections in humans and domesticated animals.Discussion: Ivermectin's mechanism of action involves binding to ligand-gated ion channel receptors including glutamate, GABA, and glycine, resulting in parasitic paralysis and death. Due to varying expression of these ion channel receptors in vertebrate species, ivermectin toxicity is rarely reported in mammals. Ivermectin is also a substrate for P-glycoprotein, which limits its neurological toxicity in humans. Genetic polymorphisms in P-glycoprotein or coadministration of P-glycoprotein inhibitors may increase the neurotoxicity of ivermectin. Other toxic effects of ivermectin after therapeutic oral use include edema, rash, headache, and ocular complaints. Most of these effects are mild and short in duration. Ivermectin exhibits antiviral effects in-vitro at very high concentrations. This has led to suggestions of ivermectin as a potential treatment for SARS-CoV-2 (COVID-19) infection, although the drug's pharmacokinetic parameters reduce the likelihood that high concentrations of the drug can be achieved in-vivo.Conclusion: Due to concern for adverse events, specifically neurotoxicity, as well as a paucity of supporting evidence, the use of ivermectin as a routine treatment or preventive measure for COVID-19 infection is not recommended at this time.


Subject(s)
COVID-19 , Ivermectin , Animals , Antiparasitic Agents/therapeutic use , Antiparasitic Agents/toxicity , Antiviral Agents , COVID-19/drug therapy , Humans , Ivermectin/therapeutic use , Ivermectin/toxicity , Mammals , SARS-CoV-2
6.
JAMA Intern Med ; 182(4): 426-435, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1704290

ABSTRACT

Importance: Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19. Evidence-based data to recommend either for or against the use of ivermectin are needed. Objective: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19. Design, Setting, and Participants: The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease. Interventions: Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging. Main Outcomes and Measures: The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events. Results: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group). Conclusions and Relevance: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04920942.


Subject(s)
COVID-19 , Ivermectin , Adult , Disease Progression , Female , Hospital Mortality , Humans , Ivermectin/adverse effects , Ivermectin/therapeutic use , Middle Aged , SARS-CoV-2 , Treatment Outcome
7.
Future Microbiol ; 17: 339-350, 2022 03.
Article in English | MEDLINE | ID: covidwho-1686353

ABSTRACT

Aims: Ivermectin is a safe, inexpensive and effective early COVID-19 treatment validated in 20+ random, controlled trials. Having developed combination therapies for Helicobacter pylori, the authors present a highly effective COVID-19 therapeutic combination, stemming from clinical observations. Patients & methods: In 24 COVID-19 subjects refusing hospitalization with high-risk features, hypoxia and untreated moderate to severe symptoms averaging 9 days, the authors administered this novel combination of ivermectin, doxycycline, zinc and vitamins D and C. Results & conclusions: All subjects resolved symptoms (in 11 days on average), and oxygen saturation improved in 24 h (87.4% to 93.1%; p = 0.001). There were no hospitalizations or deaths, less than (p < 0.002 or 0.05, respectively) background-matched CDC database controls. Triple combination therapy is safe and effective even when used in outpatients with moderate to severe symptoms. Clinical Trial Registration: NCT04482686 (ClinicalTrial.gov).


Subject(s)
COVID-19 , Ivermectin , COVID-19/drug therapy , Drug Therapy, Combination , Humans , Hypoxia/drug therapy , Ivermectin/therapeutic use , Leprostatic Agents/therapeutic use , SARS-CoV-2 , Treatment Outcome
8.
Ther Innov Regul Sci ; 56(3): 382-385, 2022 05.
Article in English | MEDLINE | ID: covidwho-1682774

ABSTRACT

In treatment or prevention of COVID-19, ivermectin is not approved by the United States (US) Food and Drug Administration (FDA). Nonetheless, in the US, prescriptions of ivermectin by healthcare providers have increased > tenfold from 3589 per week pre-COVID-19 to 39,102. Ivermectin is FDA approved for animals to treat parasites and for humans to treat intestinal strongyloidiasis and onchocerciasis orally, and ectoparasites and skin conditions topically. It is not a benign drug, with reported side effects including cutaneous, gastrointestinal, and cardiovascular symptoms. The evidence to support ivermectin to treat or prevent COVID-19 includes some basic research and inconsistent clinical observations that contribute to the formulation of a hypothesis of efficacy in COVID-19. At present, data from peer-reviewed published randomized trials of sufficient size, dose, and duration to reliably test the hypothesis of the most plausible small to moderate benefits on clinically relevant endpoints are sparse. In addition to the US FDA, the US National Institutes of Health, World Health Organization, and European Medicines Agency have all advised against ivermectin for treatment or prevention of COVID-19 outside of randomized trials. For ivermectin in treatment or prevention of COVID-19, healthcare providers should reassure all patients that if sufficient evidence were to emerge, then this drug could be considered a therapeutic innovation and regulatory authorities would approve the drug. In the meanwhile, we strongly recommend a moratorium on the prescription of ivermectin for the treatment or prevention of COVID-19 except in randomized trials to provide the most reliable test of the hypothesis.


Subject(s)
COVID-19 , Ivermectin , Animals , COVID-19/drug therapy , Humans , Ivermectin/adverse effects , Ivermectin/therapeutic use , Prescriptions , SARS-CoV-2
10.
Eur J Med Res ; 27(1): 21, 2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1666676

ABSTRACT

The global COVID-19 pandemic has affected the world's population by causing changes in behavior, such as social distancing, masking, restricting people's movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of COVID-19 is 150-200 µg/kg twice daily. As ivermectin adoption for COVID-19 increased, the Food and Drug Administration (FDA) issued a warning on its use during the pandemic. However, the drug remains of interest to clinicians and has shown some promise in observational studies. This narrative reviews the toxicological profile and some potential therapeutic effects of ivermectin. Based on the current dose recommendation, ivermectin appears to be safe with minimum side effects. However, serious questions remain about the effectiveness of this drug in the treatment of patients with COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Repositioning , Ivermectin/adverse effects , Ivermectin/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/pharmacokinetics , Clinical Trials as Topic , Humans , Ivermectin/administration & dosage , Ivermectin/pharmacokinetics , Pre-Exposure Prophylaxis/methods
11.
Int J Antimicrob Agents ; 59(3): 106542, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1654507

ABSTRACT

A key element for the prevention and management of coronavirus disease 2019 is the development of effective therapeutics. Drug combination strategies offer several advantages over monotherapies. They have the potential to achieve greater efficacy, to increase the therapeutic index of drugs and to reduce the emergence of drug resistance. We assessed the in vitro synergistic interaction between remdesivir and ivermectin, both approved by the US Food and Drug Administration, and demonstrated enhanced antiviral activity against severe acute respiratory syndrome coronavirus-2. Whilst the in vitro synergistic activity reported here does not support the clinical application of this combination treatment strategy due to insufficient exposure of ivermectin in vivo, the data do warrant further investigation. Efforts to define the mechanisms underpinning the observed synergistic action could lead to the development of novel treatment strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Ivermectin/pharmacology , Ivermectin/therapeutic use
12.
Eur J Clin Pharmacol ; 78(5): 733-753, 2022 May.
Article in English | MEDLINE | ID: covidwho-1653434

ABSTRACT

PURPOSE: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has affected millions all over the world and has been declared pandemic, as of 11 March 2020. In addition to the ongoing research and development of vaccines, there is still a dire need for safe and effective drugs for the control and treatment against the SARS-CoV-2 virus infection. Numerous repurposed drugs are under clinical investigations whose reported adverse events can raise worries about their safety. The aim of this review is to illuminate the associated adverse events related to the drugs used in a real COVID-19 setting along with their relevant mechanism(s). METHOD: Through a literature search conducted on PubMed and Google Scholar database, various adverse events suspected to be induced by eight drugs, including dexamethasone, hydroxychloroquine, chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, ivermectin, and tocilizumab, administered in COVID-19 patients in clinical practice and studies were identified in 30 case reports, 3 case series, and 10 randomized clinical trials. RESULTS: Mild, moderate, or severe adverse events of numerous repurposed and investigational drugs caused by various factors and mechanisms were observed. Gastrointestinal side effects such as nausea, abdominal cramps, diarrhea, and vomiting were the most frequently followed by cardiovascular, cutaneous, and hepatic adverse events. Few other rare adverse drug reactions were also observed. CONCLUSION: In light of their ineffectiveness against COVID-19 as evident in large clinical studies, drugs including hydroxychloroquine, lopinavir/ritonavir, and ivermectin should neither be used routinely nor in clinical studies. While lack of sufficient data, it creates doubt regarding the reliability of chloroquine and favipiravir use in COVID-19 patients. Hence, these two drugs can only be used in clinical studies. In contrast, ample well-conducted studies have approved the use of remdesivir, tocilizumab, and dexamethasone under certain conditions in COVID-19 patients. Consequently, it is significant to establish a strong surveillance system in order to monitor the proper safety and toxicity profile of the potential anti-COVID-19 drugs with good clinical outcomes.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Antiviral Agents/adverse effects , COVID-19/drug therapy , Chloroquine/adverse effects , Dexamethasone/adverse effects , Humans , Hydroxychloroquine/adverse effects , Ivermectin/therapeutic use , Lopinavir/adverse effects , Reproducibility of Results , Ritonavir/pharmacology , SARS-CoV-2
14.
J Clin Epidemiol ; 144: 43-55, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1587326

ABSTRACT

OBJECTIVE: The objective of this systematic review is to summarize the effects of ivermectin for the prevention and treatment of patients with COVID-19 and to assess inconsistencies in results from individual studies with focus on risk of bias due to methodological limitations. METHODS: We searched the L.OVE platform through July 6, 2021 and included randomized trials (RCTs) comparing ivermectin to standard or other active treatments. We conducted random-effects pairwise meta-analysis, assessed the certainty of evidence using the GRADE approach and performed sensitivity analysis excluding trials with risk of bias. RESULTS: We included 29 RCTs which enrolled 5592 cases. Overall, the certainty of the evidence was very low to low suggesting that ivermectin may result in important benefits. However, after excluding trials classified as "high risk" or "some concerns" in the risk of bias assessment, most estimates of effect changed substantially: Compared to standard of care, low certainty evidence suggests that ivermectin may not reduce mortality (RD 7 fewer per 1000) nor mechanical ventilation (RD 6 more per 1000), and moderate certainty evidence shows that it probably does not increase symptom resolution or improvement (RD 14 more per 1000) nor viral clearance (RD 12 fewer per 1000). CONCLUSION: Ivermectin may not improve clinically important outcomes in patients with COVID-19 and its effects as a prophylactic intervention in exposed individuals are uncertain. Previous reports concluding important benefits associated with ivermectin are based on potentially biased results reported by studies with substantial methodological limitations. Further research is needed.


Subject(s)
COVID-19 , Ivermectin , Bias , COVID-19/drug therapy , Humans , Ivermectin/therapeutic use , Respiration, Artificial , SARS-CoV-2
15.
Clin Exp Dermatol ; 47(5): 867-872, 2022 May.
Article in English | MEDLINE | ID: covidwho-1566278

ABSTRACT

BACKGROUND: Lockdowns and physical distancing have dramatically limited the circulation of SARS-CoV-2 and other common communicable infections. However, little is known about their impact on head lice and scabies. AIM: To assess the impact of the 2020 French National lockdowns (17 March-11 May 2020, and 30 October-15 December 2020) and physical distancing recommendations (from February 2020) on the dynamics of head lice and scabies infestations. METHODS: The weekly sales of topical head lice treatments, topical scabies treatments and oral ivermectin were extracted from the database of the healthcare science company IQVIA (60% of all French retail pharmacies) and analysed over a 5-year period (March 2016-December 2020). A periodic regression model was fitted to drug sales before the COVID-19 period (2016-2019) and extrapolated to compare the observed sales in 2020 to the expected sales. RESULTS: A decrease of the sales of tracer topical treatments for head lice and scabies was observed from March 2020, synchronously with the first French national lockdown. For the period March-December 2020, the mean reduction in observed vs. expected sales for head lice and scabies topical treatments was 44% and 14%, respectively. By contrast, although there was an observed decrease in oral ivermectin sales after March 2020, it was much lower (4%), probably because of studies reporting the potential positive effects of this drug on COVID-19 infection. CONCLUSION: COVID-19 lockdown and physical distancing reduce circulation of head lice and scabies in France. Further studies are needed to assess the long-term impact of these social behaviour changes.


Subject(s)
COVID-19 , Lice Infestations , Pediculus , Scabies , Animals , COVID-19/epidemiology , Communicable Disease Control , Humans , Ivermectin/therapeutic use , Lice Infestations/drug therapy , Lice Infestations/epidemiology , Pandemics , SARS-CoV-2 , Scabies/drug therapy , Scabies/epidemiology , Scabies/prevention & control
17.
J Cosmet Dermatol ; 21(1): 24-26, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1537839
18.
Clin Nurse Spec ; 36(1): 16-19, 2022.
Article in English | MEDLINE | ID: covidwho-1537599
19.
J Med Virol ; 94(4): 1473-1480, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1527445

ABSTRACT

Ivermectin has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. It is unknown whether this inhibition of SARS-CoV-2 replication correlates with improved clinical outcomes. To assess the effectiveness and safety of ivermectin in hospitalized patients with COVID-19. A total of 286 patients with COVID-19 were included in the study. Univariate analysis of the primary mortality outcome and comparisons between treatment groups were determined. Logistic regression and propensity score matching (PSM) was used to adjust for confounders. Patients in the ivermectin group received 2 doses of Ivermectin at 200 µg/kg in addition to usual clinical care on hospital Days 1 and 3. The ivermectin group had a significantly higher length of hospital stay than the control group; however, this significance did not maintain on multivariable logistic regression analysis. The length of intensive care unit (ICU) stay and duration of mechanical ventilation were longer in the control group. However, a mortality benefit was not seen with ivermectin treatment before and after PSM (p values = 0.07 and 0.11, respectively). ICU admission, and intubation rate were not significantly different between the groups (p = 0.49, and p = 1.0, respectively). No differences were found between groups regarding the length of hospital stay, ICU admission, intubation rate, and in-hospital mortality.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Ivermectin/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Hospital Mortality , Humans , Intensive Care Units , Ivermectin/administration & dosage , Length of Stay/statistics & numerical data , Logistic Models , Male , Middle Aged , Propensity Score , Prospective Studies , Respiration, Artificial , Safety-net Providers , Young Adult
20.
Biochim Biophys Acta Mol Basis Dis ; 1868(2): 166294, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1525694

ABSTRACT

Ivermectin (IVM) is an FDA approved macrocyclic lactone compound traditionally used to treat parasitic infestations and has shown to have antiviral potential from previous in-vitro studies. Currently, IVM is commercially available as a veterinary drug but have also been applied in humans to treat onchocerciasis (river blindness - a parasitic worm infection) and strongyloidiasis (a roundworm/nematode infection). In light of the recent pandemic, the repurposing of IVM to combat SARS-CoV-2 has acquired significant attention. Recently, IVM has been proven effective in numerous in-silico and molecular biology experiments against the infection in mammalian cells and human cohort studies. One promising study had reported a marked reduction of 93% of released virion and 99.98% unreleased virion levels upon administration of IVM to Vero-hSLAM cells. IVM's mode of action centres around the inhibition of the cytoplasmic-nuclear shuttling of viral proteins by disrupting the Importin heterodimer complex (IMPα/ß1) and downregulating STAT3, thereby effectively reducing the cytokine storm. Furthermore, the ability of IVM to block the active sites of viral 3CLpro and S protein, disrupts important machinery such as viral replication and attachment. This review compiles all the molecular evidence to date, in review of the antiviral characteristics exhibited by IVM. Thereafter, we discuss IVM's mechanism and highlight the clinical advantages that could potentially contribute towards disabling the viral replication of SARS-CoV-2. In summary, the collective review of recent efforts suggests that IVM has a prophylactic effect and would be a strong candidate for clinical trials to treat SARS-CoV-2.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Repositioning , Ivermectin/therapeutic use , SARS-CoV-2/drug effects , Virus Replication/drug effects , Animals , Antiparasitic Agents/pharmacology , Antiparasitic Agents/therapeutic use , Antiviral Agents/pharmacology , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/metabolism , Humans , Ivermectin/pharmacology , Karyopherins/metabolism , SARS-CoV-2/physiology
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