Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A

White, Kris M.; Rosales, Romel; Yildiz, Soner; Kehrer, Thomas; Miorin, Lisa; Moreno, Elena; Jangra, Sonia; Uccellini, Melissa B.; Rathnasinghe, Raveen; Coughlan, Lynda; Martínez-Romero, Carles; Batra, Jyoti; Rojc, Ajda; Bouhaddou, Mehdi; Fabius, Jacqueline M.; Obernier, Kirsten; Déjosez, Marion; Guillén, María José; Losada, Alejandro; Avilés, Pablo; Schotsaert, Michael; Zwaka, Thomas P.; Vignuzzi, Marco; Shokat, Kevan M.; Krogan, Nevan J.; Garcı́a-Sastre, Adolfo

doi:10.1126/science.abf4058

Cited by 285 publications

(333 citation statements)

References 58 publications

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“…To gain insights into interacting residues responsible for negative free energy, the discovery studio visualizer was utilized, and the key residues seen were THR [29]. Recently, the drug plitidepsin was proven to possess antiviral activity on SARS-CoV-2 virus in invitro with 27.5-fold times higher than Remdesivir, with less toxicity [30]. This study would reveal the new possible mechanism of action that could explain its therapeutic role to reduce the viral replication.…”

Section: Ensemble Molecular-docking Simulationsmentioning

confidence: 99%

Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors

et al. 2021

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Currently, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected people among all countries and is a pandemic as declared by the World Health Organization (WHO). SARS-CoVID-2 main protease is one of the therapeutic drug targets that has been shown to reduce virus replication, and its high-resolution 3D structures in complex with inhibitors have been solved. Previously, we had demonstrated the potential of natural compounds such as serine protease inhibitors eventually leading us to hypothesize that FDA-approved marine drugs have the potential to inhibit the biological activity of SARS-CoV-2 main protease. Initially, field-template and structure–activity atlas models were constructed to understand and explain the molecular features responsible for SARS-CoVID-2 main protease inhibitors, which revealed that Eribulin Mesylate, Plitidepsin, and Trabectedin possess similar characteristics related to SARS-CoVID-2 main protease inhibitors. Later, protein–ligand interactions are studied using ensemble molecular-docking simulations that revealed that marine drugs bind at the active site of the main protease. The three-dimensional reference interaction site model (3D-RISM) studies show that marine drugs displace water molecules at the active site, and interactions observed are favorable. These computational studies eventually paved an interest in further in vitro studies. Finally, these findings are new and indeed provide insights into the role of FDA-approved marine drugs, which are already in clinical use for cancer treatment as a potential alternative to prevent and treat infected people with SARS-CoV-2.

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Section: Ensemble Molecular-docking Simulationsmentioning

confidence: 99%

Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors

et al. 2021

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“…A small clinical benefit was observed when they were administered in COVID-19 patients very early after infection, enabling therapeutic antibodies to receive an Emergency Use Authorization for the treatment of mild to moderate COVID-19 patients with high risk of disease progression (Chen et al, 2021;Weinreich et al, 2021). Several antiviral drug targets including SARS-CoV proteases PLpro or 3CLpro are currently in development (Dai et al, 2020), while the recent mapping of SARS-CoV-2 proteomic interactions during viral replication (Gordon et al, 2020) helped identify host proteins that may prove to be useful antiviral drug targets (White et al, 2021).…”

Section: Mixed Success Obtained By Repurposing Antiviral Drugs and Hope For New Therapeuticsmentioning

confidence: 99%

Highlights from a year in a pandemic

Mérad

Vabret

2021

Journal of Experimental Medicine

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COVID-19 has emerged as one of the worst pandemics in recent history and has exposed the weaknesses of healthcare systems worldwide. Here, we reflect on the lessons learned from a year in a pandemic. We discuss the extraordinary scientific advances made in our understanding of a new disease, the failed and successful attempts to halt its progression, and the impact of the pandemic on the scientific discourse within the global community.

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“…The lack of drugs 379 makes it even more imperative that we find multiple ways to reduce new infections. If we can stop the virus from infecting the uninfected then the virus will not have access to new hosts and progeny viruses will not be produced in yet another host.…”

Section: Add Decision System Is Far Beyond Optical Signal Detection and Image Analysismentioning

confidence: 99%

Aptamers for Detection and Diagnostics (ADD): Can mobile systems process optical data from aptamer sensors to identify molecules indicating presence of SARS-CoV-2 virus? Should healthcare explore aptamers as drugs for prevention as well as its use as adjuvants with antibodies and vaccines?

Datta

2021

Preprint

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Proposed SARS-CoV-2 surveillance tool using a mobile app for non-invasive monitoring of humans and animals. <p>Engineering a biomedical device as a low-cost, non-invasive, detection, and diagnostic platform for surveillance of infections in humans, and animals. The system embraces the IoT <i>“digital by design”</i> metaphor by incorporating elements of connectivity, data sharing and (secure) information arbitrage. Using an array of aptamers to bind viral targets may help in detection, diagnostics, and potentially prevention in case of SARS-CoV-2. The ADD tool may become part of a broader platform approach.</p>

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Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A

Cited by 285 publications

References 58 publications

Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors

Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors

Highlights from a year in a pandemic

Aptamers for Detection and Diagnostics (ADD): Can mobile systems process optical data from aptamer sensors to identify molecules indicating presence of SARS-CoV-2 virus? Should healthcare explore aptamers as drugs for prevention as well as its use as adjuvants with antibodies and vaccines?

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