Targeting the Fusion Process of SARS-CoV-2 Infection by Small Molecule Inhibitors

Park, Seung Bum; Irvin, Parker; Hu, Zongyi; Khan, Mohsin; Hu, Xin; Zeng, Qiru; Chen, Catherine; Xu, Miao; Leek, Madeleine; Zang, Ruochen; Case, James Brett; Zheng, Wei; Ding, Siyuan; Liang, T. Jake

doi:10.1128/mbio.03238-21

Cited by 13 publications

(12 citation statements)

References 63 publications

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“…2B ). VSV was reported to not be sensitive to E-64d treatment [11]. Consistently, all four calpain inhibitors were substantially less inhibitory against VSV infection ( Fig.…”

Section: Resultssupporting

confidence: 73%

Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target

Zeng

Antia

Puray-Chavez

et al. 2022

Preprint

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Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (Mpro), which plays an essential role in processing viral polyproteins. In this study, we found that calpain inhibitors potently inhibited the infection of a chimeric vesicular stomatitis virus (VSV) encoding the SARS-CoV-2 spike protein, but not Mpro. In contrast, calpain inhibitors did not exhibit antiviral activities towards the wild-type VSV with its native glycoprotein. Genetic knockout of calpain-2 by CRISPR/Cas9 conferred resistance of the host cells to the chimeric VSV-SARS-CoV-2 virus and a clinical isolate of wild-type SARS-CoV-2. Mechanistically, calpain-2 facilitates SARS-CoV-2 spike protein-mediated cell attachment by positively regulating the cell surface levels of ACE2. These results highlight an Mpro-independent pathway targeted by calpain inhibitors for efficient viral inhibition. We also identify calpain-2 as a novel host factor and a potential therapeutic target responsible for SARS-CoV-2 infection at the entry step.

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“…2B ). VSV was reported to not be sensitive to E-64d treatment [11]. Consistently, all four calpain inhibitors were substantially less inhibitory against VSV infection ( Fig.…”

Section: Resultssupporting

confidence: 73%

Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target

Zeng

Antia

Puray-Chavez

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…We used an established S protein-mediated cell-cell fusion assay to explore the possible mechanism where HR1MFd inhibits SARS-CoV-2 infection by blocking SARS-CoV-2 S protein-mediated fusion ( 20 ). In the assay, 293T cells coexpressing SARS-CoV-2 D614G S protein and EGFP (293T/EGFP/S) were used as the effector cells, and ACE2 expressing Caco-2 or Huh-7 cells were used as the target cells.…”

Section: Resultsmentioning

confidence: 99%

Novel Engineered SARS-CoV-2 HR1 Trimer Exhibits Improved Potency and Broad-Spectrum Activity against SARS-CoV-2 and Its Variants

Chen

Dang

2022

J Virol

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“…S1 ). CCZ, a reported chemical that could block SARS-CoV-2 fusion [38] , was also examined ( Fig. 1 B).…”

Section: Resultsmentioning

confidence: 99%

Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion

Lin

et al. 2022

Biomedicine & Pharmacotherapy

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Targeting the Fusion Process of SARS-CoV-2 Infection by Small Molecule Inhibitors

Abstract: SARS-CoV-2 is an enveloped virus that requires membrane fusion for entry into host cells. Since the fusion process is relatively conserved among enveloped viruses, we tested our HCV fusion inhibitors, dichlorcyclizine and fluoxazolevir, against SARS-CoV-2.

Cited by 13 publications

References 63 publications

Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target

Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target

Novel Engineered SARS-CoV-2 HR1 Trimer Exhibits Improved Potency and Broad-Spectrum Activity against SARS-CoV-2 and Its Variants

Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion

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