Unraveling the antiviral activity of plitidepsin against SARS-CoV-2 by subcellular and morphological analysis

Bioactive natural products in COVID-19 therapy

“…(Rodon et al, 2021). Sachse et al (2022) showed that plitidepsin is highly effective at inhibiting SARS-CoV-2 replication in a dose-dependent manner in Vero E6 cells at IC 50 values of 0.0052 μM for D614G variants, 0.0039 μM for Delta variants, and 0.0043 μM for Omicron variants. Furthermore, White et al (2021) showed that plitidepsin can inhibit SARS-CoV-2 replication in Vero E6 cells, hACE2-293T cells and pneumocyte-like cells at IC 50 values of 0.00070, 0.00073, and 0.0016 μM, respectively, via targeting the host protein eEF1A.…”

A comprehensive insight into current control of COVID-19: Immunogenicity, vaccination, and treatment.

“…Plitidepsin is an anti-tumor agent showing promising results in preclinical studies against SARS-CoV-2. The antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known host protein eEF1A (eukaryotic translation elongation factor 1 alpha), which could reduce the future virus resistance to antiviral agents [262] , [263] , [264] .…”

Focus on Marine Animal Safety and Marine Bioresources in Response to the SARS-CoV-2 Crisis

“…In vivo data obtained from the infection of hACE2-sensitized or hACE2-transgenic mouse further supported antiviral effect of plitidepsin against SARS-CoV-2 [ 111 ]. Further investigation of the antiviral activity of plitidepsin on SARS-CoV-2 by transmission electron microscopy and immunohistochemistry was performed to examine its effect on viral replication [ 129 ]. It was evident that plitidepsin treatment induced the disappearance of DMVs structure for viral genome replication, and the absence of viral particle distribution in single-membrane vesicles, in the large vacuole, and on the extracellular side of the plasma membrane in Vero E6 cells at 24–D48 h post infection.…”

“…It was evident that plitidepsin treatment induced the disappearance of DMVs structure for viral genome replication, and the absence of viral particle distribution in single-membrane vesicles, in the large vacuole, and on the extracellular side of the plasma membrane in Vero E6 cells at 24–D48 h post infection. In addition, the viral N protein and dsRNA were not detected by immunostaining in plitidepsin-treated Vero E6 cells at 48 h post infection [ 129 ]. A more recent study showed that plitidepsin can virtually bind to the main protease of SARS-CoV-2 and inhibit its activity [ 130 ].…”