Therapeutic potential of natural alkaloid emetine against emerging COVID-19 and future viral pandemics

• Published in: European journal of medicinal chemistry reports Vol. 12; p. 100173
• Main Authors: Dinda, Biswanath, Dinda, Subhajit, Dinda, Manikarna, Sarma, Indrajit Sil, Majumdar, Santanu, Saha, Shekhar
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.12.2024; Elsevier
• Subjects: Anti-SARS-CoV-2 drug; COVID-19; Emetine; Immunomodulatory; Isoquinoline alkaloid; PAH inhibitor; COVID-19; Isoquinoline alkaloid; Anti-SARS-CoV-2 drug; Emetine; PAH inhibitor; Immunomodulatory
• ISSN: 2772-4174; 2772-4174
• DOI: 10.1016/j.ejmcr.2024.100173

The outbreak of COVID-19 pandemic caused by the infection of SARS-CoV-2, has become a global crisis, threatening public health and disrupting global economy. Until now, effective therapeutics against COVID-19 and other coronavirus diseases are in high demand. Several antiviral strategies of drug discovery have identified many small molecules with potent anti-COVID-19 activity. Emetine, one of the main alkaloids of Carapichea ipecacuanha, has been found to exhibit potent antiviral activity against SARS-CoV-2, and other human coronaviruses, multiple RNA and DNA viruses at low nanomolar concentrations in different cell lines. In silico analysis reveals that emetine directly disrupts the activities of SARS-CoV-2 S-protein with host ACE2, and of RdRp-, 3CL-, PL-,and N- proteins. Moreover, emetine shows potent anti-inflammatory and anti-pulmonary arterial hypertensive properties by down-regulating the p38, ERK1/2, NF-κB and RhoA/Rho-kinase/CyPA/Bsg signaling pathways. At low doses, emetine is effective for treatment of COVID-19 patients and other viral infections in rodents. This review discusses the current findings on the antiviral efficacy of emetine against the emerging SARS-CoV-2 and other corona, RNA and DNA viruses, as well as its immunoregulatory pathways and clinical potential in COVID-19 infection for its development as antiviral prodrugs to treat current COVID-19 and future viral pandemics. [Display omitted] •Emetine inhibits SARS-CoV-2 and other respiratory virus infections at low non-toxic concentrations.•Emetine targets the activities of viral S-, 3 CL-, PL-, RdRp- and host ACE2 proteases.•Emetine potently inhibits hypoxia-induced PAH disorder by down-regulation of Rho-kinase/ CyPA/Bsg pathway.•Emetine inhibits HIF-1α /-2α expression for suppression of NF-κB-dependent cytokines production.•Emetine at low doses is effective in treatment of COVID-19 infection.