Emetine and Related Alkaloids

Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations

“…3 B and C). The data corroborate the reported structural requirement ( Grollman, 1966b ; Grollman, 1966a ; Grollman, 1968 ; Grollman and Jarkovsky, 1975 ; Grollman, 1970 ) for ipecac alkaloids to inhibit protein synthesis, namely the 1R, 11bS-configurations.

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“…Antiviral treatment options against COVID-19 are limited and evidence of the efficacy of available antiviral treatments could not be reproduced consistently in recent clinical studies ( Abdool Karim and Devnarain, 2022 ). These considerations have generated interest in exploring the therapeutic efficacy of small molecules like emetine, a natural alkaloid used in primarily as an amebicide ( Grollman and Jarkovsky, 1975 ) but recently investigated for its antiviral properties towards SARS-CoV-2 ( Choy et al., 2020 ; Bojkova et al., 2020 ; Jan et al., 2021 ; Wang et al., 2020a ). Considering its unique mechanisms of action, emetine may fulfill the demand for a drug with broad-range antiviral activity and potential for synergism in combination regimens ( Valipour, 2022 ; Bleasel and Peterson, 2020b ; Bleasel and Peterson, 2020a ).…”

Transport by the (Na+, K+) ATPase: Modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line

“…from six separate experiments, with triplicate monolayers assayed per condition in each experiment. but was also observed after addition of the structurally unrelated alkaloid emetine, another protein synthesis inhibitor (Grollman and Jarkovsky, 1975). Monolayers exposed to 2 pM emetine for 24 hours exhibited a twofold stimulation of ouabain-sensitive "Rb+ uptake compared with controls (Table 6).…”

Characterization of Aurintricarboxylic Acid (ATA) Interactions with Plasma Transporter Protein and SARS-CoV-2 Viral Targets: Correlation of Functional Activity and Binding Energetics

“…The synthesis of ATA traces its origin to 1892 as the primary product of a condensation reaction between salicylic acid and formaldehyde in the presence of sulfuric acid and nitrite ion [16]. Multiple applications have been reported since its discovery, including seminal studies conducted during the 1960s and 1970s [17] that explored ATA as an inhibitor of protein synthesis in eukaryotes while elucidating specific mechanisms of several antiviral and antibiotic compounds at the ribosomal level [18][19][20][21][22][23][24][25][26]. Harnessing insights gained from parallel investigations on emetine [17][18][19]24,27], Grollman and colleagues focused particular attention on the initiation of viral protein synthesis as a target for anti-viral drug design.…”

“…Multiple applications have been reported since its discovery, including seminal studies conducted during the 1960s and 1970s [17] that explored ATA as an inhibitor of protein synthesis in eukaryotes while elucidating specific mechanisms of several antiviral and antibiotic compounds at the ribosomal level [18][19][20][21][22][23][24][25][26]. Harnessing insights gained from parallel investigations on emetine [17][18][19]24,27], Grollman and colleagues focused particular attention on the initiation of viral protein synthesis as a target for anti-viral drug design. These researchers demonstrated that triphenylmethane dyes such as ATA inhibit initiation of protein synthesis [21] and prevent the attachment of viral RNA to ribosomes isolated from rabbit reticulocytes [20,23].…”