Indomethacin: an exploratory study of antiviral mechanism and host-pathogen interaction in COVID-19

Abstract

Introduction COVID-19, a dreadful pandemic that has impacted human life like no other pathogenic invasion, has claimed the lives of over 100 million people. The need for effective treatment strategies is still a subject of intense research considering the rapidly evolving genome and continental diversity. Indomethacin is administered mostly as co-treatment for affected patients as a non-steroidal anti-inflammatory drug (NSAID). However, the underlying mechanism of action is unresolved. This study explores the basal mechanism of indomethacin and potency in alleviating the damage caused by SARS-CoV-2 and discusses the experimental and clinical efficacy in recent studies. Areas covered The literature search and system biology-based network formation were employed to describe the potent effects and risks associated with indomethacin in in-vitro, in-vivo, and clinical studies. This study also highlights the plausible mechanism of antiviral action of indomethacin with its apparent viral protein targets. The SARS-CoV-2 protein, the interacting host proteins, and the effect of indomethacin on this interactome as a standalone treatment or as part of a co-therapy strategy are particularly emphasized using network modeling. Expert opinion Indomethacin has demonstrated excellent clinical endpoint characteristics in several studies, and we recommend that it be utilized in the treatment of mild-to-moderate COVID patients.

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19

“…Direct evidence for the antiviral efficacy of indomethacin, but not of aspirin, against SARS-CoV-2 was provided in cellular models and in vivo in an infected canine model [ 90 ], suggesting that the effect is independent of anti-inflammatory action. A very recent review has shown, with system biology-based modeling, that the action of indomethacin against SARS-CoV-2 depends on the fact that prostaglandin synthetase is related to the action of some structural proteins, so that the inhibition of the former blocks the function of the latter, which are involved in the replication of viral RNA [ 91 ].…”

The effect of ramatroban on cytokine and thrombotic storms in Covid-19

“…PGs trigger the release of pro-inflammatory cytokines, activation of Th cells (Th1 and Th17), recruitment of immune cells, and increase expression of pro-inflammatory genes (Ogletree et al 2022 ). PGs are chiefly inhibited by non-steroidal anti-inflammatory drugs (NSAIDs) through the blocking of cyclooxygenase enzymes (COXs), which are involved in the synthesis of PGs (Shekhar et al 2022 ). NSAIDs reduce inflammation by selective or non-selective blocking activity of COX2 or COX1/2, respectively (Shekhar et al 2022 ).…”

“…PGs are chiefly inhibited by non-steroidal anti-inflammatory drugs (NSAIDs) through the blocking of cyclooxygenase enzymes (COXs), which are involved in the synthesis of PGs (Shekhar et al 2022 ). NSAIDs reduce inflammation by selective or non-selective blocking activity of COX2 or COX1/2, respectively (Shekhar et al 2022 ). COX2 is stimulated and up-regulated during SARS-CoV-2 infection (Ogletree et al 2022 ).…”

“…PGD2 acts on prostanoid receptors (DP1 and DP2), which induce bronchoconstriction and inflammation through activation of type 2 immune response (Th2). TXA2 exerts prothrombotic activity and increases inflammation in SARS-CoV-2 infection (Shekhar et al 2022 ). Pro-inflammatory cytokines mainly IL-1β activate the expression of endothelial and platelet TXA2 causing immunothrombosis (Shekhar et al 2022 ).…”

“…TXA2 exerts prothrombotic activity and increases inflammation in SARS-CoV-2 infection (Shekhar et al 2022 ). Pro-inflammatory cytokines mainly IL-1β activate the expression of endothelial and platelet TXA2 causing immunothrombosis (Shekhar et al 2022 ). Therefore, dual inhibitors of PGD2 and TXA2 may reduce the risk of immunothrombosis and the development of cytokine and thrombotic storms in Covid-19.…”