Prashant Ramesh Chakkarwar1
Coronavirus disease-19 (COVID-19) is the deadliest pandemic that the whole world
is facing today. COVID-19 is different from normal flu by its two lethal
manifestations which includes deadly pneumonia which may lead to acute
respiratory distress syndrome (ARDS) due to hyper-inflammation of alveolar
tissues and pulmonary intravascular coagulopathy (PIC).1,2 It is noteworthy here
to mention that both these lethal manifestations of COVID-19 are due to
abnormally high levels of pro-inflammatory cytokines like interleukin (IL) - 1β, IL
- 6, and tumour necrosis factor (TNF) - α, termed as “cytokine storm.”3,4
There is a certain link between pro-inflammatory cytokines like IL - 1β, IL - 6,
and TNF - α and its pro-coagulatory influence on coagulation pathway mediated
by tissue factor that binds and activate factor VII, leading to formation of tissue
factor – VII a complexes which results in the activation of clotting factor X and
IX.4 Recently the researchers in China and some European countries have found
raised level of pro-inflammatory cytokines particularly IL - 6 in severe cases of
COVID-19. They also found raised D-dimer, fibrinogen levels and prothrombin time
in moderate to severe COVID-19 cases.5,6
Both of these lethal manifestations of COVID-19 – ARDS and PIC are linked to
raised levels of pro-inflammatory cytokines, particularly, IL - 6. It is not very clear
that the pro-inflammatory action of cytokines is mediated through leukotrienes as
the biochemical assay for leukotrienes are not widely available but possibility of
this probable mechanism cannot be ruled out. Hence, development of any
molecule with ability to inhibit pro-inflammatory cytokines, particularly IL-6 may
be able to tame the lethal nature of COVID-19, and may ultimately reduce the
mortality of this deadly pandemic.
Montelukast sodium is such molecule which has capacity to inhibit proinflammatory
cytokines such as IL - 1β, IL - 6, and TNF - α.7 Montelukast sodium
is leukotriene receptor antagonist that inhibits the cysteinyl leukotriene type-1
receptor. Leukotrienes modulate the production of pro-inflammatory cytokines.8
Its antagonist action on leukotriene receptors can inhibit the production of these
pro-inflammatory cytokines.
Even recent in silico study by Jacobson at Oak Ridge National Lab, was found
that excess bradykinin production may be responsible for pulmonary, cardiac,
neurological and nephrological lethal manifestations of COVID-19.9 Crimi et al.10
already found that Montelukast is effective to control bradykinin induced
bronchoconstriction. Thus, theoretically, montelukast seems to be best molecule
to deal with deadly manifestation of COVID-19 even if we go by cytokine storm
hypothesis or bradykinin hypothesis.
