Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2

Drayman, Nir; DeMarco, Jennifer K; Jones, Kohar; Azizi, Saara-Anne; Froggatt, Heather M.; Tan, Kemin; Maltseva, N.; Chen, Siquan; Nicolaescu, Vlad; Dvorkin, Steve; Furlong, Kevin; Kathayat, Rahul S.; Firpo, Mason R; Mastrodomenico, Vincent; Bruce, Emily A.; Schmidt, Madaline M; Jedrzejczak, R.; Muñoz-Alía, Miguel Ángel; Schuster, Brooke; Nair, V. P.; Han, Kyu-Yeon; O’Brien, Amornrat; Τοματσίδου, Αναστασία; Meyer, Bjoern; Vignuzzi, Marco; Missiakas, Dominique; Botten, Jason; Brooke, Christopher B.; Lee, Hyun; Baker, Susan C.; Mounce, Bryan C.; Heaton, Nicholas S.; Severson, William; Palmer, Kenneth E.; Dickinson, Bryan C.; Joachimiak, A.; Randall, Glenn; Tay, Savaş

doi:10.1126/science.abg5827

Cited by 182 publications

(174 citation statements)

References 53 publications

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“…Conversely, some MS DMTs could be repurposed to manage COVID-19-associated immune dysregulation. Clinical trials are already ongoing to evaluate IFN-B, fingolimod, dimethylfumarate; additionally, masitinib (a tyrosine-kinase inhibitor that showed efficacy in phase 2B/3 trials for progressive MS) has been recently highlighted as a potent Coronavirus inhibitor (188).…”

Section: Discussionmentioning

confidence: 99%

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

et al. 2021

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Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host’s genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host’s response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.

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Section: Discussionmentioning

confidence: 99%

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

et al. 2021

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“…For these reasons, M pro becomes a high-profile drug target for the development of broad-spectrum antivirals. Structurally disparate compounds including FDA-approved drugs and bioactive compounds have been reported as M pro inhibitors 6 , 7 , 8 , 9 , 10 , several of which also have in vivo antiviral efficacy against SARS-CoV-2 11 , 12 , 13 , 14 , 15 .…”

Section: Introductionmentioning

confidence: 99%

Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays

Tan

Choza

et al. 2022

Acta Pharmaceutica Sinica B

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“…The uncertainty of the coronavirus disease 2019 (COVID-19) pandemic situation remains elusive, although great success has been accomplished with the rapid development of protective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are currently no effective drugs for the treatment of COVID-19, although clinical trials and case reports involving antiviral and antiparasitic agents have yielded promising results that warrant further investigation [ 1 , 2 ]. Herbal medicines have a long history of vindicated clinical efficacy against infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment

Wang

et al. 2021

Molecules

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Glycyrrhizic acid (GA), also known as glycyrrhizin, is a triterpene glycoside isolated from plants of Glycyrrhiza species (licorice). GA possesses a wide range of pharmacological and antiviral activities against enveloped viruses including severe acute respiratory syndrome (SARS) virus. Since the S protein (S) mediates SARS coronavirus 2 (SARS-CoV-2) cell attachment and cell entry, we assayed the GA effect on SARS-CoV-2 infection using an S protein-pseudotyped lentivirus (Lenti-S). GA treatment dose-dependently blocked Lenti-S infection. We showed that incubation of Lenti-S virus, but not the host cells with GA prior to the infection, reduced Lenti-S infection, indicating that GA targeted the virus for infection. Surface plasmon resonance measurement showed that GA interacted with a recombinant S protein and blocked S protein binding to host cells. Autodocking analysis revealed that the S protein has several GA-binding pockets including one at the interaction interface to the receptor angiotensin-converting enzyme 2 (ACE2) and another at the inner side of the receptor-binding domain (RBD) which might impact the close-to-open conformation change of the S protein required for ACE2 interaction. In addition to identifying GA antiviral activity against SARS-CoV-2, the study linked GA antiviral activity to its effect on virus cell binding.

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Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2

Cited by 182 publications

References 53 publications

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays

Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment

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