CORONZOT – a novel COVID-19 treatment!
On April 22nd, Silkim Pharma filed a pre-Investigational New Drug (PIND) meeting request with the U.S. Food and Drug Administration (FDA) for its drug candidate CORONZOT in the treatment of COVID-19 patients with moderate-to-severe symptoms.
On May 5th, FDA responded positively to the meeting request and on May 16th Silkim Pharma received FDA’s written response (meeting summary). The response includes FDA’s advice and guidance on the planned clinical study.
Following the FDA’s advice, Silkim Pharma plans to submit an IND application for CORONZOT to be evaluated as a potential addition to the current standard of care treatment for COVID-19.
“We thank the FDA for reviewing our application in such a short time, for accepting our meeting request and for providing the guidance we requested, and we look forward to finalizing the IND and then moving towards conducting clinical studies of CORONZOT for COVID-19. The scientific and medical literature, our experience in inflammatory pathologies, and the favorable safety experience of our drug candidate support the exploration of CORONZOT as a therapy for COVID-19 patients who are hospitalized with moderate to severe symptoms,” stated Silkim Pharma CEO Dror Chevion.
While the human body is under attack by SARS-CoV-2 coronavirus, causing the COVID-19 disease, the exaggerated reaction of the body’s immune system, triggered by the virus, is deadly! This phenomenon is called Cytokine Release Syndrome (CRS), or “Cytokine Storm”.
Under certain circumstances, an immune system, usually aimed at identifying external invaders and eliminating them, releases an overwhelming number of cytokines – the signaling molecules secreted by various cells in order to mediate the innate immune response. This tsunami of cytokines, in turn, activates more and more cells within the organism, progressing to hyper-inflammatory condition, often with life-threatening pulmonary involvement. This systemic hyperinflammation results in inflammatory lymphocytic and monocytic infiltration of lungs and heart, causing the life-threatening Acute Respiratory Distress Syndrome (ARDS) and cardiac failure.
In some cases, the cytokine storm leads to Disseminated Intravascular Coagulation (DIC) – a potentially fatal condition, in which blood clots form throughout the body, blocking small blood vessels. According to some reports, amid the COVID-19 patients in Wuhan, these features were observed in 71% of non-survivors and in 0.6% of those recovered from the disease.
One of the pivotal factors to be “incriminated” in this process is overaccumulation of labile, redox-active iron. It catalyses the production of Reactive Oxygen-derived Species (ROS), responsible for triggering, maintaining and promoting pro-inflammatory processes. Consequently, hyperferritinemia, the excessive blood level of ferritin - the main iron storage protein, produced in response to iron overload, was shown to serve as a pro-inflammatory mediator and poor prognosis marker. Besides, iron, hijacked from a host organism, is essential for multiplication of the virus.
“Coronzot”, a novel family of medications against COVID-19, recently developed by the Israeli pharmaceutical startup company Silkim Pharma Ltd., employs a novel mechanism based on sequestration of the labile iron, introducing an ion of gallium or zinc, in limited amounts, instead.
Application of Coronzot renders a quadruple effect against the COVID-19 disease:
(i) Sequestration of iron mitigates cytokine storm by suppressing the production of the pro-inflammatory cytokines, and restrains virus multiplication.
(ii) Sequestration of iron also inhibits the activity of the viral lungs- and heart-attacking proteins, thus mitigating ARDS, lungs and heart failure;
(iii) Insertion of gallium instead of iron to iron-dependent proteins inhibits replication of viruses and promotes the apoptosis (self-destruction) of the already invaded cells;
(iv) Release of zinc directly to the site of infection contributes to suppression of the pro-inflammatory reactions and inhibits the activity of enzymes essential for invasion, pathogenesis, replication and virulence of the SARS-CoV coronavirus.