Abstract: Life Research doi: 10.53388/life2022-0202-302 Life Research Submit a manuscript: https://www.tmrjournals.com/tmr/lr 01 Life Research doi: 10.53388/life2022-0202-302 Review The pharmacological mechanism of quercetin as adjuvant therapy of COVID-19 Wahyu Choirur Rizky Mushtaq 1 , Muhammad Candragupta Jihwaprani 1 , Avicena Al Kindi1, Arif Nur Muhammad Ansori 2 , Mazhar 3* Abstract The emergence of novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the global outbreak and major public health concern. After the outbreak human-to-human transmission was confirmed with or without symptoms of upper and lower respiratory tract involvement. Up to date, there has been evidence that COVID-19 is beyond that of a typical pulmonary disease and revealing pathomechanics of COVID-19-associated acute respiratory distress syndrome (CARDS), which include severe inflammation and pulmonary edema leading to impaired alveolar homeostasis, and resulting in an alteration of lung physiology, lung fibrosis, inflammation of endothelium, vascular thrombosis, as well as exaggerated immune response. Concerning this pathophysiology, the use of quercetin as phytotherapeutic may merit in the management of COVID-19 patients. In this review, the authors wish to elaborate on the molecular effect of quercetin on SARS-CoV-2 by giving a detailed mechanism of quercetin against the binding of the S-protein of the virus to angiotensin-converting enzyme 2 (ACE2) receptors, the main protease (Mpro) or 3C-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRP). Recent clinical evidence supporting the use of quercetin in COVID-19 management is also discussed in this paper. Keywords: Quercetin; phytotherapeutic; COVID-19; antiviral; anti-inflammatory; anti-fibrosis