Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection

Seo, Sang Heui; Jang, Yunyueng

doi:10.3390/vaccines8040584

Cited by 56 publications

(50 citation statements)

References 52 publications

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“…By 6 dpc, mice in G3 (high virus dose/vehicle, white symbols) showed about 20% weight loss and by 8 dpc there were no survivors because they have either succumbed to the infection or had to be humanely euthanized due to severe clinical signs (lethargy, ruffled fur, labored breathing, and/or ≥25% body weight loss, Fig 2D). These observations are consistent with previous reports 20,21,24,25 . G4 mice (high virus dose/GC-376) showed similar clinical signs but such progression was delayed by about 24 h (~15% weight loss by 6 dpc).…”

Section: Modest Effect Of Gc-376 Treatment On the Clinical Outcome Ofsupporting

confidence: 94%

“…Since then, several reports have emerged and our results are in agreement with the notion that the K18-hACE2 mouse model is a suitable small animal model to study SARS-CoV-2 pathogenesis 20,21,25 . Previous reports have also shown that K18-hACE2 mice are amenable for the study of vaccines against SARS-CoV-2 24 but, to our knowledge, assessment of this mouse model for the evaluation of potential antivirals against SARS-CoV-2 was lacking.…”

Section: Effects Of Gc-376 Treatment On Sars-cov-2-induced Pathology mentioning

confidence: 98%

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Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

Cáceres

Cardenas-Garcia

Carnaccini

et al. 2021

Preprint

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The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice and produced milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls, most notably in the brain in mice challenged with a low virus dose. Although GC-376 was not sufficient to improve neither clinical symptoms nor survival, it did show a positive effect against SARS-CoV-2 in vivo. This study supports the notion that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2, and GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection.

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Section: Modest Effect Of Gc-376 Treatment On the Clinical Outcome Ofsupporting

confidence: 94%

Section: Effects Of Gc-376 Treatment On Sars-cov-2-induced Pathology mentioning

confidence: 98%

Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

Cáceres

Cardenas-Garcia

Carnaccini

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…2D). These observations are consistent with previous reports 16,17,20,21 . G4 mice (high virus dose/GC-376) showed similar clinical signs but such progression was delayed by about 24 h (~ 15% weight loss by 6 dpc).…”

Section: Effect Of Gc-376 Treatment On the Clinical Outcome In Mice Challenged With Sars-cov-2supporting

confidence: 94%

Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

Cáceres

Cardenas-Garcia

Carnaccini

et al. 2021

Sci Rep

View full text Add to dashboard Cite

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 105 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 103 TCID50/mouse. This was particularly the case in the brain where a 5-log reduction in viral titers was observed in GC-376 treated mice compared to vehicle controls. This study supports the notion that GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection and that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2.

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“…Sinovac Biotech and Sinopharm are at present conducting phase 3 trials on inactivated vaccines. [32][33][34]…”

Section: Inactivated Virus Vaccinesmentioning

confidence: 99%

COVID-19 vaccine landscape

Seneviratne

Jayarajah

Abeysuriya

et al. 2020

J of Cey Coll of Phy

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Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection

Cited by 56 publications

References 52 publications

Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

COVID-19 vaccine landscape

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