Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities

Wehbe, Zena; Wehbe, Maya; Iratni, Rabah; Pintus, Gianfranco; Zaraket, Hassan; Yassine, Hadi M.; Eid, Ali H.

doi:10.3389/fimmu.2021.663586

Cited by 29 publications

(29 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other meta-analyses have specifically examined the role of ivermectin for COVID-19 [6,17,18]. One, based on 4 trials and 397 participants, concluded that ivermectin reduced overall mortality and led to a significant clinical improvement compared to the usual therapy, but also highlighted the limitations of these conclusions due to the very low quality of the available evidence [7]. In the other two reviews, overall mortality was the only outcome considered; both studies revealed a significant reduction of the odds of mortality in ivermectin recipients compared to the controls [17,18].…”

Section: Discussionmentioning

confidence: 99%

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Cruciani¹,

Pati²,

Masiello³

et al. 2021

Diagnostics

View full text Add to dashboard Cite

Background. Ivermectin has received particular attention as a potential treatment for COVID-19. However, the evidence to support its clinical efficacy is controversial. Objectives. We undertook a new systematic review of ivermectin for the treatment and prophylaxis of COVID-19, including new primary studies, outcomes other than mortality, and grading the quality of the available evidence following the Cochrane guidance for methodology. Methods. We searched electronic databases, repository databases, and clinical trial registries (up to June 2021). The measure of treatment effect was risk difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the evidence. Results. The review includes 11 RCTs (2436 participants). The certainty of the available evidence was quite low or very low due to risk of bias, inconsistency, and imprecision. When the analysis was limited to patients with baseline mild or moderate disease (8 reports, 1283 patients), there were no differences in mortality between ivermectin and control groups (low level of certainty); in patients with baseline severe diseases (3 reports, 304 patients), the use of ivermectin significantly decreased mortality compared to the controls (RD −0.17; 95% CIs, −0.24/−0.10; p = 0.00001; low level of certainty). In terms of disease progression (to severe pneumonia, admission to intensive care unit, and/or mechanical ventilation), the results were much the same. At day 14, the rate of patients with a negative RT-PCR test was 21% higher (from 5 to 36% higher) for ivermectin recipients than it was for the controls (low quality of evidence). Three studies (736 subjects) indicated that prophylaxis with ivermectin increased the likelihood of preventing COVID-19 compared to controls (low quality of evidence). Serious adverse events were rarely reported. Conclusions. There is limited evidence for the benefit of ivermectin for COVID-19 treatment and prophylaxis, and most of this evidence is of low quality. Further evidence is needed to fine-tune potential indications and optimal treatment protocols for ivermectin as a treatment for COVID-19.

show abstract

Section: Discussionmentioning

confidence: 99%

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Cruciani¹,

Pati²,

Masiello³

et al. 2021

Diagnostics

View full text Add to dashboard Cite

show abstract

“…Ruxolitinib and baricitinib target the Janus-Kinase pathway and inhibit cytokine release [ 66 , 67 ]. The other repurposing drugs have miscellaneous effects on the viral pathogenesis and inhibit the viral growth by different mechanisms, for instance, ivermectin inhibits the nuclear transport activity, and statins targets the angiotensin-converting enzyme 2 [ 68 , 69 ]. The remdesivir, the most accepted repurposed drug for the SARS-CoV-2, inhibits the RdRp protein, therefore, inhibits the viral replication [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Repurposing of gastric cancer drugs against COVID-19

Sonkar

Doharey

Rathore

et al. 2021

Computers in Biology and Medicine

View full text Add to dashboard Cite

Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a global pandemic. Additionally, the SARS-CoV-2 infection in the patients of Gastric Cancer (GC; the third leading cause of death in the world) pose a great challenge for the health management of the patients. Since there have been uncertainties to develop a new drug against COVID-19, there is an urgent need for repurposing drugs that can target key proteins of both SARS-CoV-2 and GC. The SARS-CoV-2-RdRp protein contains the NiRAN domain, which is known to have kinase-like folds. A docking study of the FDA approved drugs against GC was performed using AutoDock 4.2 and Glide Schrodinger suite 2019 against SARS-CoV-2-RdRp protein. MMGBSA and MD simulation studies were performed to investigate the binding and stability of the inhibitors with the target protein. In this study, we have found 12 kinase inhibitors with high binding energies namely Baricitinib, Brepocitinib, Decernotinib, Fasudil, Filgotinib, GSK2606414, Peficitinib, Ruxolitinib, Tofacitinib, Upadacitinib, Pamapimod and Ibrutinib. These FDA approved drugs against GC can play a key role in the treatment of COVID-19 patients along with GC as comorbidity. We also hypothesize that JAK, ITK, Rho-associated kinases, FGFR2, FYN, PERK, TYK2, p38-MAPK and SYK kinases can be considered as key therapeutic targets in COVID-19 treatment. Taken altogether, we have proposed the SARS-CoV-2-RdRp as a potential therapeutic target through in-silico studies. However, further in-vitro and in-vivo studies are required for the validation of the proposed targets and drugs for the treatment of COVID-19 patients already suffering from GC.

show abstract

“…In 2020, Caly et al [ 164 ] found that Ivermectin is an inhibitor of SARS-CoV-2 in-vitro and though the mechanism is unknown, it is hypothesized to work by disinhibiting the virus’s evasion tactics from the host immune cells and thus abrogate sufficient viral replication and allow the host to clear it. Another suggested mechanism is the suppression of the production of Interleukin-6 (IL-6) and Tumor Necrosis Factor alpha (TNFα), two major components of the detrimental cytokine storm induced by SARS-CoV-2 [ 165 ].…”

Section: Targeting Covid-19 Therapymentioning

confidence: 99%

“…Both the Food and Drug Administration (FDA) of the United States and European Medicines Agency (EMA) have advised against its use, stating insufficient evidence for any benefit [ 166 ]. It has been highlighted that the required concentration of 5 µM to reach the anti-SARS-CoV-2 action of Ivermectin observed in vitro is fifty-fold higher than the current FDA-approved dosage (200 μg/kg) [ 165 , 166 ]. Hence, this may explain why it was not included in large-scale clinical trials such as the Solidarity trial [ 166 ].…”

Section: Targeting Covid-19 Therapymentioning

confidence: 99%

See 1 more Smart Citation

Pharmacotherapeutic agents for the management of COVID-19 patients with preexisting cardiovascular disease

Khan

Singh

Abrar

et al. 2021

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Introduction The coronavirus disease 2019 (COVID-19) pandemic is the largest public health challenge of the twenty-first century. While COVID-19 primarily affects the respiratory system, manifesting as interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also has implications for the cardiovascular system. Moreover, those admitted to hospital with severe COVID-19 are more likely to have cardiovascular comorbidities such as hypertension and diabetes mellitus. The underlying pathophysiology of why COVID-19 onset can further decline cardiac pathologies as well as trigger acute onset of new cardiac complications is not yet well understood. Areas covered In this review, the authors extensively review literature focused on the current understanding and approaches of managing patients who have underlying cardiovascular diseases and concomitant COVID-19 infection. Furthermore, the authors explore the possible cardiovascular implications of the suggested COVID-19 therapeutic agents that are used to treat this lethal disease. Expert opinion Current evidence is evolving around the many trialed pharmacotherapeutic considerations for the management of coronavirus disease 2019 (COVID-19) in patients with cardiovascular disease. While we await such data, clinicians should advocate for careful consideration of all concomitant medications for those presenting with COVID-19 on a patient-by-patient basis.

show abstract

Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities

Cited by 29 publications

References 60 publications

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis

Repurposing of gastric cancer drugs against COVID-19

Pharmacotherapeutic agents for the management of COVID-19 patients with preexisting cardiovascular disease

Contact Info

Product

Resources

About