Targeting cyclooxygenase enzyme for the adjuvant COVID-19 therapy.

ABSTRACT

Despite vigorous efforts, the COVID-19 pandemic continues to take a toll on the global health. The contemporary therapeutic regime focused on the viral spike proteins, viral 3CL protease enzyme, immunomodulation, inhibition of viral replication, and providing a symptomatic relief encouraged the repurposing of drugs to meet the urgency of treatment. Similarly, the representative drugs that proved beneficial to alleviate SARS-CoV-1, MERS-CoV, HIV, ZIKV, H1N1, and malarial infection in the past presented a sturdy candidature for ameliorating the COVID-19 therapeutic doctrine. However, most of the deliberations for developing effective pharmaceuticals proved inconsequential, thereby encouraging the identification of new pathways, and novel pharmaceuticals for capping the COVID-19 infection. The COVID-19 contagion encompasses a burst release of the cytokines that increase the severity of the infection mainly due to heightened immunopathogenicity. The pro-inflammatory metabolites, COX-2, cPLA2, and 5-LOX enzymes involved in their generation, and the substrates that instigate the origination of the innate inflammatory response therefore play an important role in intensifying and worsening of the tissue morbidity related to the coronavirus infection. The deployment of representative drugs for inhibiting these overexpressed immunogenic pathways in the tissues invaded by coronaviruses has been a matter of debate since the inception of the pandemic. The effectiveness of NSAIDs such as Aspirin, Indomethacin, Diclofenac, and Celecoxib in COVID-19 coagulopathy, discouraging the SARS viral replication, the inflammasome deactivation, and synergistic inhibition of H5N1 viral infection with representative antiviral drugs respectively, have provided a silver lining in adjuvant COVID-19 therapy. Since the anti-inflammatory NSAIDs and COXIBs mainly function by reversing the COX-2 overexpression to modulate the overproduction of pro-inflammatory cytokines and chemokines, these drugs present a robust treatment option for COVID-19 infection. This commentary succinctly highlights the various claims that support the status of immunomodulatory NSAIDs, and COXIBs in the adjuvant COVID-19 therapy.