Published anti-SARS-CoV-2 <i>in vitro</i> hits share common mechanisms of action that synergize with antivirals

Xing, Jing; Paithankar, Shreya; Liu, Ke; Uhl, Katie; Li, Xiaopeng; Ko, Meehyun; Kim, Seungtaek; Haskins, Jeremy S.; Chen, Bin

doi:10.1093/bib/bbab249

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…Lomitapide mesylate is an effective microsomal triglyceride transfer protein inhibitor for the treatment of familial hypercholesterolemia. Lomitapide mesylate was first found to exhibit antiviral activity in a drug repurposing candidate screening for COVID-19 (Xing et al, 2021). Our results demonstrated that lomitapide mesylate could inhibit SARS-CoV-2 infection in vivo.…”

Section: Discussionmentioning

confidence: 55%

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

Peng

Ding

Jiang

et al. 2021

Sci. China Life Sci.

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis. Clinical candidates with high efficacy, ready availability, and that do not develop resistance are in urgent need. Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture, there are few confirmed antiviral candidates in vivo . In this study, 94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs. Among them, 24 compounds with low cytotoxicity were selected, and of these, 17 compounds also effectively suppressed SARS-CoV-2 infection in HeLa cells transduced with human ACE2. Six compounds disturb multiple processes of the SARS-CoV-2 life cycle. Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2 infection. Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant. Except for cisatracurium, six compounds reduced hamster pulmonary viral load, and IL-6 and TNF -α mRNA when assayed at 4 d postinfection. In particular, sertraline, salinomycin, and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro , suggesting promising application for COVID-19 treatment. Supporting Information The supporting information is available online at 10.1007/s11427-021-2031-7. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Section: Discussionmentioning

confidence: 55%

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

Peng

Ding

Jiang

et al. 2021

Sci. China Life Sci.

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“…Drug repurposing of SARS-CoV-2 is one of the hottest topics in the applications of the network of SARS-CoV-2. In addition to the aforementioned works, other similar works were done for identifying drug repurposing of SARS-CoV-2. ,,− …”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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“…In the study, it was found to change the expression of mRNA levels of HMGCS1 (3-hydroxy-3-methylglutaryl-CoA synthase 1) in human lung primary small airway cells by 3–8-fold at 0.5 μM concentration. The anti- SARS-CoV-2 efficacy of monensin (EC 50 ) was predicted to be 11 μM in Vero E6 cells …”

Section: Potential Glycosylation Inhibitors For Sars-cov-2mentioning

confidence: 99%

“…The anti-SARS-CoV-2 efficacy of monensin (EC 50 ) was predicted to be 11 μM in Vero E6 cells. 34 5.1.3. Mannostatin A.…”

Section: Tunicamycin Tunicamycin Is An Antibiotic Produced Bymentioning

confidence: 99%

Exploring the Potential of Chemical Inhibitors for Targeting Post-translational Glycosylation of Coronavirus (SARS-CoV-2)

et al. 2022

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The Spike (S) protein of SARS-CoV-2 expressed on the viral cell surface is of particular importance as it facilitates viral entry into the host cells. The S protein is heavily glycosylated with 22 N-glycosylation sites and a few N-glycosylation sites. During the viral surface protein synthesis via the host ribosomal machinery, glycosylation is an essential step in post-translational modifications (PTMs) and consequently vital for its life cycle, structure, immune evasion, and cell infection. Interestingly, the S protein of SARS-CoV-2 and the host receptor protein, ACE2, are also extensively glycosylated and these surface glycans are critical for the viral–host cell interaction for viral entry. The glycosylation pathway of both virus (hijacked from the host biosynthetic machinery) and target cells crucially affect SARS-CoV-2 infection at different levels. For example, the glycosaminoglycans (GAGs) of host cells serve as a cofactor as they interact with the receptor-binding domain (RBD) of S-glycoprotein and play a protective role in host immune evasion via masking the viral peptide epitopes. Hence, the post-translational glycan biosynthesis, processing, and transport events could be potential targets for developing therapeutic drugs and vaccines. Especially, inhibition of the N-glycan biosynthesis pathway amplifies S protein proteolysis and, thus, blocks viral entry. The chemical inhibitors of SARS-CoV-2 glycosylation could be evaluated for Covid-19. In this review, we discuss the current status of the chemical inhibitors (both natural and synthetically designed inhibitors) of viral glycosylation for Covid-19 and provide a future perspective. It could be an important strategy in targeting the various emerging SARS-CoV-2 variants of concern (VOCs), as these inhibitors are postulated to aid in reducing the viral load as well as infectivity.

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Published anti-SARS-CoV-2 in vitro hits share common mechanisms of action that synergize with antivirals

Cited by 9 publications

References 35 publications

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Exploring the Potential of Chemical Inhibitors for Targeting Post-translational Glycosylation of Coronavirus (SARS-CoV-2)

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