Non‐steroidal anti‐inflammatory drugs, prostaglandins, and COVID‐19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the novel coronavirus disease 2019 (COVID-19), a highly pathogenic and sometimes fatal respiratory disease responsible for the current 2020 global pandemic. Presently, there remains no effective vaccine or efficient treatment strategies against COVID-19. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines very widely used to alleviate fever, pain, and inflammation (common symptoms of COVID-19 patients) through effectively blocking production of prostaglandins (PGs) via inhibition of cyclooxyganase enzymes. PGs can exert either proinflammatory or anti-inflammatory effects depending on the inflammatory scenario. In this review, we survey the potential roles that NSAIDs and PGs may play during SARS-CoV-2 infection and the development and progression of COVID-19.

Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy

“…The high incidence of thromboembolic events from autopsy findings suggests an important role of COVID-19–induced coagulopathy [ 91 , 92 , 93 , 94 ]. In addition to the main strategies such as targeting SARS-CoV-2 attachment and entry to human and viral replication or systemic immune responses, targeting hyper-inflammation with steroids, such as dexamethasone and non-steroidal anti-inflammatory drugs (NSAIDs) have been attempted in a number of clinical trials [ 95 ]. Among NSAIDs, the anti-platelet drug, aspirin is significantly associated with reduced risk of developing COVID-19 certainly due to anti-inflammatory and anti-coagulant effects [ 95 ].…”

“…In addition to the main strategies such as targeting SARS-CoV-2 attachment and entry to human and viral replication or systemic immune responses, targeting hyper-inflammation with steroids, such as dexamethasone and non-steroidal anti-inflammatory drugs (NSAIDs) have been attempted in a number of clinical trials [ 95 ]. Among NSAIDs, the anti-platelet drug, aspirin is significantly associated with reduced risk of developing COVID-19 certainly due to anti-inflammatory and anti-coagulant effects [ 95 ]. Thus, we speculate that aspirin may reduce NETs induced immuno-thrombotic events, and that observation of NETs formation in the course of COVID-19 clinical trials involving aspirin administration that are ongoing, would be of interest.…”

Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study

“…The WHO has indicated that there is no evidence to confirm an aggravation of COVID-19 infection with the administration of NSAIDs [30,31]. In fact, it has been reported that some NSAIDs could have some type of activity against viruses such as VZV [32], HCMV [32], HSV-1 [33], influenza virus A⁄ H1N1 subtype [34,35], VSV [36,37], EBOLA [38,39], HIV [40], JEV [41], CHIKV [42], SARS-CoV-1 [43], and recently against SARS-CoV-2 [35,44,45]. Additionally, many studies have been carried out that propose various targets for blocking virus recognition, importation and replication processes through the use of reused drugs, immunotherapies, interference strategies and various inhibitory compounds [46].…”

In silico identification of available drugs targeting cell surface BiP to disrupt SARS-CoV-2 binding and replication: Drug repurposing approach

“…Grapiprant is an anti-inflammatory prostaglandin inhibitor currently used to treat inflammatory pain by competitively inhibiting the prostaglandin E 2 (PGE 2 ) receptor protein subtype 4 (EP4) ( Nakao et al, 2007 ). EP4 is abundantly expressed on the surface of lung cells and almost all immune cells ( Robb et al, 2020 ). After PGE 2 -binging, EP4 can initiate a wide range of physiological effects including cellular differentiation, proliferation, angiogenesis, and inflammation ( Kalinski, 2012 , Konya et al, 2013 ).…”