The G614 pandemic SARS-CoV-2 variant is not more pathogenic than the original D614 form in adult Syrian hamsters

Stauft, Charles B.; Lien, Christopher Z.; Selvaraj, Prabhuanand; Li, Shufeng; Wang, Tony T.

doi:10.1016/j.virol.2021.01.005

Cited by 18 publications

(29 citation statements)

References 11 publications

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“…Over several months, the D614G mutation has become the dominant form of the virus circulating globally, with the major mutations occurring on Spike protein. However, in the animal model, it was shown that the variant G614 was not more pathogenic than the original D614 [ 76 ]. The analysis of the evolving geographical diversity in SARS-CoV-2 exhibited high similarities and no variation in the sequences of 3CL pro [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Eberle

Olivier

Amaral

et al. 2021

Viruses

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Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

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Section: Discussionmentioning

confidence: 99%

The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Eberle

Olivier

Amaral

et al. 2021

Viruses

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“…Stauft et al conducted an animal model study to evaluate the pathogenicity of D614 and G614 variants in the Spike protein. The authors showed that there was no difference in pathology in lung tissues of hamsters infected with these variants [18].…”

Section: Relation Between Viral Mutations and Severity Of Covid-19 Infectionmentioning

confidence: 98%

“…Of the 63 publications included, five were non-peer reviewed preprints [16,17,52,54,66]. Eleven articles reported in vitro, in silico or animal model studies [15,18,19,[22][23][24][25][26][27][28][29]; nineteen articles reported clinical studies [16,[37][38][39][41][42][43][44][45][46][47][48][49]51,[70][71][72][73]. The remaining 33 articles analyzed SARS-CoV-2 genomes downloaded from the GISAID or other available databases with patient status [8][9][10][11]20,21,[30][31][32][33][34][35][36]40,50,…”

Section: Study Selection and Types Of Studiesmentioning

confidence: 99%

“…Twenty-five studies reported the relation between viral mutations and virus load or infectivity of SARS-CoV-2 (Table 2), of which five articles (two in vitro/animal model studies [18,19], two studies based on SARS-CoV-2 genomes downloaded from electronic databases or community-based testing datasets (bigdata analysis) [20,21] and one clinical study [16]) showed no impact of mutations with infectivity of SARS-CoV-2. The remaining 20 studies (nine in vitro/animal model or in silico studies [15,[22][23][24][25][26][27][28][29], eight bigdata analyses [9,[30][31][32][33][34][35][36] and three clinical studies [37][38][39]) showed that SARS-CoV-2 variants were significantly associated with increase in infectivity.…”

Section: Relation Between Viral Mutation and Infectivity Of Sars-cov-2mentioning

confidence: 99%

“…Three studies (one bigdata analysis [50] and two clinical studies [17,51]) reported that the SARS-CoV-2 variants were significantly associated with decrease in severity of disease. The remaining 27 studies (one animal study [18], 22 bigdata analyses [8][9][10][11][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] and four clinical studies [70][71][72][73]) described the positive association between the different variants with severity of COVID-19 (Table 3). A clinical study by Long et al showed that infection with SARS-CoV-2 variants harboring the D614G substitution was not associated with disease severity, overall mortality, transfer to ICU, mechanical ventilation and length of stay at hospital [41].…”

Section: Relation Between Viral Mutations and Severity Of Covid-19 Infectionmentioning

confidence: 99%

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SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Dao

Hoang

Colson

et al. 2021

JCM

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Background: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro. Method: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar. Results: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory. Conclusion: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.

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Long‐term immunity in convalescent Syrian hamsters provides protection against new‐variant SARS‐CoV‐2 infection of the lower but not upper respiratory tract

Stauft

Selvaraj

Lien

et al. 2022

Journal of Medical Virology

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COVID-19 vaccines provide high levels of protection against severe disease and hospitalization due to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Vaccination may be less effective in preventing shedding of infectious viruses from otherwise immune patients. In this study, we describe breakthrough infections and shedding of infectious viruses in convalescent hamsters without significant replication in the lower respiratory tract following reinfection by Alpha and Delta variants despite high levels of circulating antibodies in sera. Using convalescent hamsters with long-term immunity (up to 1 year) following infection by ancestral SARS-CoV-2, we can model aspects of recurring COVID-19 in the context of preexisting immunity.

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The G614 pandemic SARS-CoV-2 variant is not more pathogenic than the original D614 form in adult Syrian hamsters

Cited by 18 publications

References 11 publications

The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Long‐term immunity in convalescent Syrian hamsters provides protection against new‐variant SARS‐CoV‐2 infection of the lower but not upper respiratory tract

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