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

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.