Treatment with an Anti-CK2 Synthetic Peptide Improves Clinical Response in COVID-19 Patients with Pneumonia. A Randomized and Controlled Clinical Trial

Abstract

The instrumental role of CK2 in the SARS-CoV-2 infection has pointed out this protein kinase as promising therapeutic target in COVID-19. Anti-SARS-CoV-2 activity has been reported by CK2 inhibitors in vitro ; however, no anti-CK2 clinical approach has been investigated in COVID-19. This trial aimed to explore the safety and putative clinical benefit of CIGB-325, an anti-CK2 peptide previously assessed in cancer patients. A monocentric, controlled, and therapeutic exploratory trial of intravenous CIGB-325 in adults hospitalized with COVID-19 was performed. Twenty patients were randomly assigned to receive CIGB-325 (2.5 mg/kg/day during 5-consecutive days) plus standard-of-care (10 patients) or standard-of-care alone (10 patients). Adverse events were classified by the WHO Adverse Reaction Terminology. Parametric and nonparametric statistical analyses were performed according to the type of variable. Considering the small sample size, differences between groups were estimated by Bayesian analysis. CIGB-325 induced transient mild and/or moderate adverse events such as pruritus, flushing, and rash in some patients. Both therapeutic regimens were similar with respect to SARS-CoV-2 clearance in nasopharynx swabs over time. However, CIGB-325 significantly reduced the median number of pulmonary lesions (9.5 to 5.5, p = 0.042) at day 7 and the proportion of patients with such an effect was also higher according to Bayesian analysis (pDif > 0; 0.951). Also, CIGB-325 significantly reduced the CPK ( p = 0.007) and LDH ( p = 0.028) plasma levels at day 7. Our preliminary findings suggest that this anti-CK2 clinical approach could be combined with standard-of-care in COVID-19 in larger studies.

Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection

“…CIGB-325 is a peptide-based drug capable to inhibit the CK2-mediated phosphorylation on the substrates, from clinic evidences previously assessed in cancer patients, this anti-CK2 peptide is safe and well-tolerated [16, 17, 19]. To investigate the putative therapeutic use of CIGB-325 in SARS-CoV-2 infected patients, a Phase I/II clinical trial was conducted [19].…”

“…CIGB-325 is a peptide-based drug capable to inhibit the CK2-mediated phosphorylation on the substrates, from clinic evidences previously assessed in cancer patients, this anti-CK2 peptide is safe and well-tolerated [16, 17, 19]. To investigate the putative therapeutic use of CIGB-325 in SARS-CoV-2 infected patients, a Phase I/II clinical trial was conducted [19]. Consistent with the instrumental role of CK2 in SARS-CoV-2 infection, CIGB-325 treatment showed clinical benefit as evidenced by a significant reduction of the pulmonary lesions and lesion’s extent at day 7, suggesting a potential antiviral activity in the infected lung epithelium [19].…”

“…To investigate the putative therapeutic use of CIGB-325 in SARS-CoV-2 infected patients, a Phase I/II clinical trial was conducted [19]. Consistent with the instrumental role of CK2 in SARS-CoV-2 infection, CIGB-325 treatment showed clinical benefit as evidenced by a significant reduction of the pulmonary lesions and lesion’s extent at day 7, suggesting a potential antiviral activity in the infected lung epithelium [19]. However, exploring antiviral activity on in vitro coronavirus infection models needs to be accomplished.…”

“…For instance, anti-HIV activity was reported as the peptide interferes with a putative NPM1-Rev interaction in cells and subsequently downregulates Rev-dependent gene expression [18]. Recently, a Phase I/II clinical trial with CIGB-325 showed benefits in Covid-19 patients with pneumonia with significant reduction of the pulmonary lesions and quick improvement of the clinical status at day 7 [19]. Some many aspects of disease caused by highly pathogenic human CoV can be recapitulated in animal CoV diseases.…”

Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach

“…Considering this background, CIGB-300 was tested for its safety and clinical benefits in Covid-19 patients in a phase I/II clinical trial (Cruz et al 2020 ). It reduced the number of pulmonary lesions among treated individuals.…”