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.