Different Aspects of Emetine's Capabilities as a Highly Potent SARS-CoV-2 Inhibitor against COVID-19

In the global movement to find the appropriate agents to fight the coronavirus disease of 2019 (COVID-19), emetine is one of the strongest anti-SARS-CoV-2 compounds with sub-micromolar EC₅₀ values, identified in several studies and high-throughput screening efforts. The reported anti-SARS-CoV-2 mechanisms indicate the effect of this compound on both virus-based and host-based targets. In addition to having excellent antiviral effects, emetine can relieve COVID-19 patients by reducing inflammation through inhibitory activity against NF-κB by the mechanism of IκBα phosphorylation inhibition; it can also limit the lipopolysaccharide-induced expression of pro-inflammatory cytokines TNFα, IL-1β, and IL-6. Emetine also can well reduce pulmonary arterial hypertension as an important COVID-19 complication by modulating a variety of cellular processes such as the Rho-kinase/CyPA/Bsg signaling pathway. The therapeutic value of emetine for combating COVID-19 was highlighted when in vivo pharmacokinetic studies showed that the concentration of this compound in the lungs increases significantly higher than the EC₅₀ of the drug. Despite its valuable therapeutic effects, emetine has some cardiotoxic effects that limit its use in high doses. However, high therapeutic capabilities make emetine a valuable lead compound that can be used for the design and development of less toxic anti-COVID-19 agents in the future. This Review provides a collection of information on the capabilities of emetine and its potential for the treatment of COVID-19, along with structural analysis which could be used for further research in the future.