Dual action anti‐inflammatory/antiviral isoquinoline alkaloids as potent naturally occurring anti‐SARS‐CoV‐2 agents: A combined pharmacological and medicinal chemistry perspective

Abstract In the search for compounds that inhibit the SARS‐CoV‐2 after the onset of the COVID‐19 pandemic, isoquinoline‐containing alkaloids have been identified as compounds with high potential to fight the disease. In addition to having strong antiviral activities, most of these alkaloids have significant anti‐inflammatory effects which are often manifested through the inhibition of a promising host‐based anti‐COVID‐19 target, the p38 MAPK signaling pathway. In the present review, our pharmacological and medicinal chemistry evaluation resulted in highlighting the potential of anti‐SARS‐CoV‐2 isoquinoline‐based alkaloids for the treatment of COVID‐19 patients. Considering critical parameters of the antiviral and anti‐inflammatory activities, mechanism of action, as well as toxicity/safety profile, we introduce the alkaloids emetine, cephaeline, and papaverine as high‐potential therapeutic agents for use in the treatment of COVID‐19. Although preclinical studies confirm that some isoquinoline‐based alkaloids reviewed in this study have a high potential to inhibit the SARS‐CoV‐2, their entry into drug regimens of COVID‐19 patients requires further clinical trial studies and toxicity evaluation.