Approval of Itolizumab for COVID-19: A Premature Decision or Need of The Hour?

Atal, Shubham; Fatima, Zareen; Sadasivam, Balakrishnan

doi:10.1007/s40259-020-00448-5

Cited by 20 publications

(22 citation statements)

References 19 publications

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“… 11 Therefore, IL-6 blocking agents have been effectively used for the treatment of patients with hyper inflammatory states and also approaches intended at impeding this cytokine have been rapidly endeavored. 12 …”

Section: Introductionmentioning

confidence: 99%

Inhibitory Potential of Phytochemicals on Interleukin-6-Mediated T-Cell Reduction in COVID-19 Patients: A Computational Approach

Malik

Naz

Ahmad

et al. 2021

Bioinform Biol Insights

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Background: A recent COVID-19 pandemic has resulted in a large death toll rate globally and even no cure or vaccine has been successfully employed to combat this disease. Patients have been reported with multi-organ dysfunction along with acute respiratory distress syndrome which implies a critical situation for patients and made them difficult to breathe and survive. Moreover, pathology of COVID-19 is also related to cytokine storm which indicates the elevated levels of interleukin (IL)-1, IL-6, IL-12, and IL-18 along with tumor necrosis factor (TNF)-α. Among them, the proinflammatory cytokine IL-6 has been reported to be induced via binding of severe acute respiratory syndrome coronavirus 2 (SARS)-CoV-2 to the host receptors. Methodology: Interleukin-6 blockade has been proposed to constitute novel therapeutics against COVID-19. Thus, in this study, 15 phytocompounds with known antiviral activity have been subjected to test for their inhibitory effect on IL-6. Based on the affinity prediction, top 3 compounds (isoorientin, lupeol, and andrographolide) with best scores were selected for 50 ns molecular dynamics simulation and MMGB/PBSA binding free energy analysis. Results: Three phytocompounds including isoorientin, lupeol, and andrographolide have shown strong interactions with the targeted protein IL-6 with least binding energies (−7.1 to −7.7 kcal/mol). Drug-likeness and ADMET profiles of prioritized phytocompounds are also very prominsing and can be further tested to be potential IL-6 blockers and thus benficial for COVID-19 treatment. The moelcular dynamics simulation couple with MMGB/PBSA binding free energy estimation validated conformational stability of the ligands and stronger intermolecular binding. The mean RMSD of the complexes is as: IL6-isoorientin complex (3.97 Å ± 0.77), IL6-lupeol (3.97 Å ± 0.76), and IL6-andrographolide complex (3.96 Å ± 0.77). In addition, the stability observation was affirmed by compounds mean RMSD: isoorientin (0.72 Å ± 0.32), lupeol (mean 0.38 Å ± 0.08), and andrographolide (1.09 Å ± 0.49). A similar strong agreement on systems stability was unraveled by MMGB/PBSA that found net binding net ~ −20 kcal/mol for the complexes dominated by van der Waal interaction energy. Conclusion: It has been predicted that proposing potential IL-6 inhibitors with less side effects can help critical COVID-19 patients because it may control the cytokine storm, a major responsible factor of its pathogenesis. In this study, 3 potential phytocompounds have been proposed to have inhibitory effect on IL-6 that can be tested as potential therapeutic options against SARS-CoV-2.

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Section: Introductionmentioning

confidence: 99%

Inhibitory Potential of Phytochemicals on Interleukin-6-Mediated T-Cell Reduction in COVID-19 Patients: A Computational Approach

Malik

Naz

Ahmad

et al. 2021

Bioinform Biol Insights

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“…A randomised trial of 30 patients with moderate and severe COVID‐19 recently concluded in India 15 . According to the initial data, none of the 20 patients assigned to itolizumab died, while 3 of the 10 individuals given usual care died 30 . While new trials are available, we speculate that the timely administration of itolizumab, guided by biomarkers, can interrupt the hyperinflammatory cascade and might prevent morbidity and mortality related to the cytokine release syndrome.…”

Section: Discussionmentioning

confidence: 88%

“…15 According to the initial data, none of the 20 patients assigned to itolizumab died, while 3 of the 10 individuals given usual care died. 30 While new trials are available, we speculate that the timely administration of itolizumab, guided by biomarkers, can interrupt the hyperinflammatory cascade and might prevent morbidity and mortality related to the cytokine release syndrome. The safety and effectiveness of itolizumab in COVID-19 will be evaluated in a global, multinational phase III, randomised clinical trial (ClinicalTrials.gov number: NCT04605926).…”

Section: Discussionmentioning

confidence: 95%

Treatment of COVID‐19 patients with the anti‐CD6 antibody itolizumab

Caballero¹,

Filgueira²,

Betancourt³

et al. 2020

Clin & Trans Imm

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Objectives COVID‐19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on mature T lymphocytes which is a crucial regulator of the T‐cell activation. Itolizumab is a humanised antibody targeting CD6. Nonclinical and clinical data in autoimmune diseases indicate that it lowers multiple cytokines primarily involving the Th1/Th17 pathway. The primary objective of this study was to assess the impact of itolizumab in arresting the lung function deterioration of COVID‐19 patients. Secondary objectives included safety, duration of ventilation, 14‐day mortality and evaluation of interleukin 6 concentration. Methods Patients with confirmed SARS‐CoV‐2 received itolizumab in combination with other therapies included in the national protocol for COVID‐19. Results Seventy critical, severe or moderate patients were treated with itolizumab in 10 Cuban hospitals. Median age was 68, and 94% had comorbidities. After 72 h, most patients improved the PO2/FiO2 ratio and reduced FiO2 requirements. Ventilation time was 8 days for critical and 1 day for severe cases. Ten patients had related adverse events while 3 subjects developed related serious events. In 30 patients, interleukin 6 decreased in individuals with high level and did not change in those with lower concentration. Fourteen‐day lethality rate was 4% and 18% for moderate and severe patients, respectively. The proportion of moderate or severe patients with ventilation or death at day 14 was 9.8%. Time to treatment, neurological manifestations and biomarkers such as NLR were significantly associated with higher lethality. Conclusions The opportune administration of itolizumab might interrupt the hyperinflammatory cascade and prevent COVID‐19 morbidity and mortality.

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“…Coronavirus disease (COVID- 19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, Hubei Province, China on 17 November 2019, and was designated as a risk to public health on 30 January 2020 [1][2][3]. On 11 March 2020, the World Health Organization declared COVID-19 a pandemic [4].…”

Section: Introductionmentioning

confidence: 99%

Computational Chemistry to Repurposing Drugs for the Control of COVID-19

Hassanzadeganroudsari

Ahmadi

Rashidi

et al. 2021

Biologics

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Thus far, in 2021, 219 countries with over 175 million people have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a positive sense, single-stranded RNA virus, and is the causal agent for coronavirus disease (COVID-19). Due to the urgency of the situation, virtual screening as a computational modeling method offers a fast and effective modality of identifying drugs that may be effective against SARS-CoV-2. There has been an overwhelming abundance of molecular docking against SARS-CoV-2 in the last year. Due to the massive volume of computational studies, this systematic review has been created to evaluate and summarize the findings of existing studies. Herein, we report on computational articles of drugs which target, (1) viral protease, (2) Spike protein-ACE 2 interaction, (3) RNA-dependent RNA polymerase, and (4) other proteins and nonstructural proteins of SARS-CoV-2. Based on the studies presented, there are 55 identified natural or drug compounds with potential anti-viral activity. The next step is to show anti-viral activity in vitro and translation to determine effectiveness into human clinical trials.

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Approval of Itolizumab for COVID-19: A Premature Decision or Need of The Hour?

Cited by 20 publications

References 19 publications

Inhibitory Potential of Phytochemicals on Interleukin-6-Mediated T-Cell Reduction in COVID-19 Patients: A Computational Approach

Inhibitory Potential of Phytochemicals on Interleukin-6-Mediated T-Cell Reduction in COVID-19 Patients: A Computational Approach

Treatment of COVID‐19 patients with the anti‐CD6 antibody itolizumab

Computational Chemistry to Repurposing Drugs for the Control of COVID-19

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