Generation of a VeroE6 Pgp gene knock out cell line and its use in SARS-CoV-2 antiviral study

Zhu, Yuao; Binder, Joe; Yurgelonis, Irina; Rai, Devendra; Lazarro, Sarah; Costales, Chester; Kobylarz, Keith; McMonagle, Patricia; Steppan, Claire M.; Aschenbrenner, Lisa; Anderson, Annaliesa S.; Cardin, Rhonda D.

doi:10.1016/j.antiviral.2022.105429

Cited by 8 publications

(3 citation statements)

References 19 publications

(32 reference statements)

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“…SIMR3030 exhibited potent antiviral activity in this established model with an IC 50 value of 0.0596 μg/mL. The potent antiviral activity of SIMR3030 in Vero-ACE2 cells compared to parental Vero-E6 cells could be mediated through the increased drug efflux through the high expression of P-gp (P-glycoprotein) in Vero-E6 cells [ 49 ]. Interestingly, despite the significant difference between SARS-CoV-2 PLpro and MERS-CoV -PLpro, SIMR3030 inhibited MERS-CoV-infected Vero-E6 cell replication with an IC 50 of 6.206 μg/mL.…”

Section: Discussionmentioning

confidence: 99%

Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19

Hersi

Sebastian

Tarazi

et al. 2023

European Journal of Medicinal Chemistry

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Section: Discussionmentioning

confidence: 99%

Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19

Hersi

Sebastian

Tarazi

et al. 2023

European Journal of Medicinal Chemistry

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“…In drug treatment, EIDD-2801 (an orally bioavailable prodrug of EIDD-1931) and EIDD-1931 (an active form of molnupiravir) treatment in Vero E6 cells did not show significant IC 50 value changes (Vangeel et al, 2022). Thus, it may be due to without treatment of P-glycoprotein inhibitor (P-pg, drug efflux inhibitor), which enhanced IC 50 values by 10–100-fold for nirmatrelvir and remdesivir in Vero E6 cells and experimental conditions (Vangeel et al, 2022; Imai et al, 2023; Fiaschi et al, 2022; Zhu et al, 2022).…”

Section: Textmentioning

confidence: 99%

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

Cho¹,

Shin²,

Yang³

et al. 2023

Preprint

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The ongoing emergence of SARS-CoV-2 Omicron subvariants and their rapid worldwide spread pose a threat to public health. From November 2022 to February 2023, newly emerged Omicron subvariants, including BQ.1.1, BF.7, BA.5.2, XBB.1, XBB.1.5, and BN.1.9, became prevalent global strains (>5% global prevalence). These Omicron subvariants are resistant to several therapeutic antibodies. Thus, the antiviral activities of current drugs such as remdesivir, molnupiravir, and nirmatrelvir, which target highly conserved regions of SARS-CoV-2, against newly emerged Omicron subvariants need to be evaluated. We assessed the antiviral efficacy of the drugs using half maximal inhibitory concentration (IC50) against human isolated 23 Omicron subvariants and four former SARS-CoV-2 variants of concern (VOC) and compared them with the antiviral efficacy of these drugs against the SARS-CoV-2 reference strain (hCoV/Korea/KCDC03/2020). Maximal IC50 fold changes of remdesivir, molnupiravir, and nirmatrelvir were 1.9- (BA.2.75.2), 1.2- (B.1.627.2), and 1.4-fold (BA.2.3), respectively, compared to median IC50 values of the reference strain. Moreover, median IC50-fold changes of remdesivir, molnupiravir, and nirmatrelvir against the Omicron variants were 0.96, 0.4, and 0.62, similar to 1.02, 0.88, and 0.67, respectively, of median IC50-fold changes for previous VOC. Although K90R and P132H in Nsp 5, and P323L, A529V, G671S, V405F, and ins823D in Nsp 12 mutations were identified, these amino acid substitutions did not affect drug antiviral activity. Altogether, these results indicated that the current antivirals retain antiviral efficacy against newly emerged Omicron subvariants, and provide comprehensive information on the antiviral efficacy of these drugs. Keywords: SARS-CoV-2, Omicron subvariant, remdesivir, molnupiravir, nirmatrelvir, antiviral activity

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“…Furthermore, VeroE6 cells typically express high levels of the efflux transporter multi-drug resistance 1 (MDR1) or P-glycoprotein (P-gp). As a consequence, antiviral assays are typically performed in presence of an efflux inhibitor to avoid misinterpretation of the data ( Zhu et al, 2022 ). A final drawback of the VeroE6 cell line is that SARS-CoV-2 acquires several genetic changes, when propagated in these cells, especially in the Spike protein ( Liu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Development of a robust and convenient dual-reporter high-throughput screening assay for SARS-CoV-2 antiviral drug discovery

et al. 2023

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Generation of a VeroE6 Pgp gene knock out cell line and its use in SARS-CoV-2 antiviral study

Cited by 8 publications

References 19 publications

Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19

Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

Development of a robust and convenient dual-reporter high-throughput screening assay for SARS-CoV-2 antiviral drug discovery

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