The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2

Ryu, Dong-Kyun; Kang, Bobin; Noh, Hanmi; Woo, Sun-Je; Nuijten, Patricia M.; Kim, Jong-In; Seo, Ji-Min; Kim, Cheol-Min; Kim, Min‐Soo; Yang, Eun Ae; Lim, Gippeum; Kim, Seong-Gyu; Eo, Su-Kyeong; Choi, Jung-ah; Song, Manki; Oh, Sang-Ho; Chung, Hyo-Young; Tijsma, Aloys; Baalen, Carel A. van; Kwon, Kisung; Lee, Sang Yup

doi:10.1016/j.bbrc.2021.09.023

Cited by 43 publications

(43 citation statements)

References 19 publications

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“…Regdanvimab decreased viral load in the upper and lower respiratory tracts in animal models of SARS-CoV-2 infection [ 2 ]. The antibody showed antiviral activity against newly emerging variants of SARS-CoV-2 (Gamma, Delta and its associated variants [ 14 ] and 501Y.V2 or B.1.351 [ 15 ]). In vitro, regdanvimab was able to neutralize these variants, albeit showing reduced binding affinity to their RBD.…”

Section: Scientific Summarymentioning

confidence: 99%

“…In vitro, regdanvimab was able to neutralize these variants, albeit showing reduced binding affinity to their RBD. In transgenic mouse models inoculated with these variants, regdanvimab at clinically relevant dosages improved survival rate, reduced weight loss and decreased viral load in the upper and lower respiratory tracts [ 14 , 15 ].…”

Section: Scientific Summarymentioning

confidence: 99%

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Regdanvimab: First Approval

Syed

2021

Drugs

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Section: Scientific Summarymentioning

confidence: 99%

Section: Scientific Summarymentioning

confidence: 99%

Regdanvimab: First Approval

Syed

2021

Drugs

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“…This lineage has been classified into three sublineages viz. B.1.617.1, B.1.617.2, and B.1.617.3 [34]. All the sublineages are found to be harboring Several studies have confirmed the role of this RBD-ACE2 interaction in the viral entry process [18][19][20].…”

Section: Introductionmentioning

confidence: 78%

“…This lineage has been classified into three sublineages viz. B.1.617.1, B.1.617.2, and B.1.617.3 [34]. All the sublineages are found to be harboring diverse mutations within the RBD of the S protein [32].…”

Section: Introductionmentioning

confidence: 98%

Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight

Khan

Baig

Mondal

et al. 2021

Viruses

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The recent emergence of novel SARS-CoV-2 variants has threatened the efforts to contain the COVID-19 pandemic. The emergence of these “variants of concern” has increased immune escape and has supplanted the ancestral strains. The novel variants harbored by the B.1.617 lineage (kappa and delta) carry mutations within the receptor-binding domain of spike (S) protein (L452R + E484Q and L452R + T478K), the region binding to the host receptor. The double mutations carried by these novel variants are primarily responsible for an upsurge number of COVID-19 cases in India. In this study, we thoroughly investigated the impact of these double mutations on the binding capability to the human host receptor. We performed several structural analyses and found that the studied double mutations increase the binding affinity of the spike protein to the human host receptor (ACE2). Furthermore, our study showed that these double mutants might be a dominant contributor enhancing the receptor-binding affinity of SARS-CoV-2 and consequently making it more stable. We also investigated the impact of these mutations on the binding affinity of two monoclonal antibodies (Abs) (2-15 and LY-CoV555) and found that the presence of the double mutations also hinders its binding with the studied Abs. The principal component analysis, free energy landscape, intermolecular interaction, and other investigations provided a deeper structural insight to better understand the molecular mechanism responsible for increased viral transmissibility of these variants.

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“…Ferrets are a suitable model of COVID-19 for features such as viral replication kinetics, virus dissemination and transmission compared to other small animal models [28, 29]. Clinical presentation is absent or mild, and histopathology findings usually show variable grades of inflammatory infiltration in the upper and/or lower respiratory tract, which is not homogeneous among reports [22, 30, 31]. However, a large share of these studies relate to the original strains of SARS-CoV-2, and little is yet known about the susceptibility of the ferret to VOCs.…”

Section: Discussionmentioning

confidence: 99%

Influenza infection in ferrets with SARS-CoV-2 infection history

Melo

Peters

Dijken

et al. 2022

Preprint

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Non-pharmaceutical interventions (NPIs) to contain the SARS-CoV-2 pandemic drastically reduced human-to-human interactions, decreasing the circulation of other respiratory viruses as well. As a consequence, influenza virus circulation – normally responsible for 3-5 million hospitalizations per year globally – was significantly reduced. With downscaling the NPI countermeasures, there is a concern for increased influenza disease, particularly in individuals suffering from post-acute effects of SARS-CoV-2 infection. To investigate this possibility, we performed a sequential influenza H1N1 infection 4 weeks after an initial SARS-CoV-2 infection in the ferret model. Upon H1N1 infection, ferrets that were previously infected with SARS-CoV-2 showed an increased tendency to develop clinical symptoms compared to the control H1N1 infected animals. Histopathological analysis indicated only a slight increase for type II pneumocyte hyperplasia and bronchitis. The effects of the sequential infection thus appeared minor. However, ferrets were infected with B.1.351-SARS-CoV-2, the beta variant of concern, which replicated poorly in our model. The histopathology of the respiratory organs was mostly resolved 4 weeks after SARS-CoV-2 infection, with only reminiscent histopathological features in the upper respiratory tract. Nevertheless, SARS-CoV-2 specific cellular and humoral responses were observed, confirming an established infection. Thus, there may likely be a SARS-CoV-2 variant-dependent effect on the severity of disease upon a sequential influenza infection as we observed mild effects upon a mild infection. It, however, remains to be determined what the impact is of more virulent SARS-CoV-2 variants.ImportanceDuring the COVID-19 pandemic, the use of face masks, social distancing and isolation were not only effective in decreasing the circulation of SARS-CoV-2, but also in reducing other respiratory viruses such as influenza. With less restrictions, influenza is slowly returning. In the meantime, people still suffering from long-COVID, could be more vulnerable to an influenza virus infection and develop more severe influenza disease. This study provides directions to the effect of a previous SARS-CoV-2 exposure on influenza disease severity in the ferret model. This model is highly valuable to test sequential infections under controlled settings for translation to humans. We could not induce clear long-term COVID-19 effects as SARS-CoV-2 infection in ferrets was mild. However, we still observed a slight increase in influenza disease severity compared to ferrets that had not encountered SARS-CoV-2 before. It may therefore be advisable to include long-COVID patients as a risk group for influenza vaccination.

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The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2

Cited by 43 publications

References 19 publications

Regdanvimab: First Approval

Regdanvimab: First Approval

Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight

Influenza infection in ferrets with SARS-CoV-2 infection history

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