SCIENCE

Targeting inflammation resolution, a new therapeutic paradigm using the body’s own ability to modulate inflammatory responses, thus controlling inflammation without inducing immunosuppression
(a “pro-resolving” effect).

 

 

LAU-7b as an antiviral and inflammation-controlling treatment in COVID-19

SARS-CoV2 is a novel coronavirus identified as the cause of the coronavirus disease 2019 (COVID-19) that began in Wuhan, China in late 2019, and rapidly qualified as a pandemic. No effective therapy currently exists for treatment. While most patients with COVID-19 disease are thought to have a favorable prognosis, older patients and those with chronic underlying conditions may have worse outcomes with hyper-inflammation in the lungs and rapid progression to acute respiratory distress syndrome (ARDS) that may result in a requirement for mechanical ventilation, thus creating an unsustainable burden for the health care system and a rapidly escalating crisis. One of the main mechanisms for ARDS is cytokine storm, a deadly uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines and chemokines.

Anti-inflammatory treatments that aggressively inhibit inflammation are less expected to have a significant benefit during the viral response phase of the disease (mild to moderate disease), when the immune response is required for to effectively fight the infection and prevent its escalation to lung hyper-inflammatory phase. Indeed, recent results from a clinical study with dexamethasone corticosteroid therapy in hospitalized COVID-19 patients showed a reduction in death incidence by one-third in critically ill patients receiving invasive mechanical ventilation, by one-fifth in patients receiving oxygen without invasive mechanical ventilation, but it did not reduce mortality in patients not receiving respiratory support at randomization.

Inspired by the many similarities between the aberrant inflammatory response in the lung of exacerbating CF patients and the pathogenesis of pulmonary complications associated with the COVID-19 infection, and by its recently discovered antiviral properties against coronavirus, LAU-7b is being explored as a dual antiviral and inflammation-controlling treatment for COVID-19 disease.

LAU-7b, which showed potent antiviral effects in-vitro against both SARS-CoV-2 and MERS-CoV coronaviruses, is believed to work in COVID-19 by modulating key membrane lipids in conjunction with pro-resolving pathways ERK1/2, NF-kB and cPLA2, which also play a role in virus cellular entry, replication and avoidance of host defense system. By inhibiting these molecular pathways, LAU-7b may not only interfere with virus spread in the body, but also prevent the escalation of the pro-inflammatory response resulting during the infection process. Furthermore, LAU-7b showed its ability to maintain lung oxygenation and reduce inflammation in a preclinical model of ARDS, as well as preventing the cytokine storm in a preclinical model of septic shock.

Due to its antiviral properties and its pro-resolving effects on inflammation, LAU-7b is being proposed as a COVID-19 treatment to reduce the infection severity, maintain a balanced immune-inflammatory response and prevent the disease progression toward an ARDS, particularly in patients at risk because of their age, underlying conditions, or both.