*6.8. Therapeutic Effects of PTS against COVID-19 Infection*

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), triggered a major setback to global human health and the economy in the 21st century [125]. Resveratrol was tested and proved to have effective therapeutic value against MERS-CoV infection by decreasing cell death [126]. Screening studies have indicated that stilbenes inhibit complex formation between the spike protein and ACE-2 receptor, thereby blocking viral entry into the host cell [127]. Based on these studies, stilbene derivatives could be considered important drug candidates for COVID-19 [127]. PTS has been demonstrated to actively inhibit SARS-CoV-2 virus replication in infected African green monkey kidney cells. Antiviral activity was seen for up to five rounds of replication, which indicates a long-lasting therapeutic effect.

Moreover, in human primary bronchial epithelial cells isolated from healthy volunteers, PTS showed an antiviral effect for up to 48 h after infection. These data promote the use of PTS as a potent drug against COVID-19 and warrant further clinical trials to prove its antiviral efficacy early in COVID-19 [125]. Furthermore, PTS, co-administered with zinc, has also been identified as a potential COVID-19 adjuvant therapy for managing moderate–severe disease [128]. However, further clinical trials are required to back the pharmacotherapeutic potential of PTS. COVID-19 patients with comorbidities related to metabolic syndromes, such as diabetes, obesity, hypertension, and cardiovascular disease, have low levels of the HO antioxidant enzyme. Higher HO-1 expression has been associated with reduced susceptibility to COVID-19 infection [129]. Considering that COVID-19 patients are susceptible to the induction of overt inflammatory processes and cytokine storms, PTS treatment could exert anti-inflammatory and cytoprotective effects by increasing HO-1 expression [130].
