scholarly journals Scalable, methanol‐free manufacturing of the SARS‐CoV‐2 receptor‐binding domain in engineered Komagataella phaffii

2021 ◽  
Author(s):  
Neil C. Dalvie ◽  
Andrew M. Biedermann ◽  
Sergio A. Rodriguez‐Aponte ◽  
Christopher A. Naranjo ◽  
Harish D. Rao ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Komagataella Phaffii

scholarly journals Scalable, methanol-free manufacturing of the SARS-CoV-2 receptor binding domain in engineered Komagataella phaffii

2021 ◽  
Author(s):  
Neil C Dalvie ◽  
Andrew M Biedermann ◽  
Sergio A Rodriguez-Aponte ◽  
Christopher A Naranjo ◽  
Harish D Rao ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Large Scale ◽  
Scale Up ◽  
Binding Domain ◽  
Vaccine Antigen ◽  
Scale Production ◽  
Receptor Binding Domain ◽  
Methanol Induction ◽  
Vaccine Candidates ◽  
Komagataella Phaffii

Prevention of COVID-19 on a global scale will require the continued development of high-volume, low-cost platforms for the manufacturing of vaccines to supply on-going demand. Vaccine candidates based on recombinant protein subunits remain important because they can be manufactured at low costs in existing large-scale production facilities that use microbial hosts like Komagataella phaffii (Pichia pastoris). Here, we report an improved and scalable manufacturing approach for the SARS-CoV-2 spike protein receptor binding domain (RBD); this protein is a key antigen for several reported vaccine candidates. We genetically engineered a manufacturing strain of K. phaffii to obviate the requirement for methanol-induction of the recombinant gene. Methanol-free production improved the secreted titer of the RBD protein by >5x by alleviating protein folding stress. Removal of methanol from the production process enabled scale up to a 1,200 L pre-existing production facility. This engineered strain is now used to produce an RBD-based vaccine antigen that is currently in clinical trials and could be used to produce other variants of RBD as needed for future vaccines.

Destabilizing the Structural Integrity of SARS-CoV2 Receptor Proteins by Curcumin Along with Hydroxychloroquine: An Insilco Approach for a Combination Therapy

2020 ◽  
Author(s):  
Akhileshwar Srivastava ◽  
Divya Singh
Keyword(s):  
Binding Energy ◽  
Combination Therapy ◽  
Receptor Binding ◽  
Structural Integrity ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Receptor Proteins ◽  
Main Protease ◽  
The Stability ◽  
Therapeutic Activities

Presently, an emerging disease (COVID-19) has been spreading across the world due to coronavirus (SARS-CoV2). For treatment of SARS-CoV2 infection, currently hydroxychloroquine has been suggested by researchers, but it has not been found enough effective against this virus. The present study based on in silico approaches was designed to enhance the therapeutic activities of hydroxychloroquine by using curcumin as an adjunct drug against SARS-CoV2 receptor proteins: main-protease and S1 receptor binding domain (RBD). The webserver (ANCHOR) showed the higher protein stability for both receptors with disordered score (<0.5). The molecular docking analysis revealed that the binding energy (-24.58 kcal/mol) of hydroxychloroquine was higher than curcumin (-20.47 kcal/mol) for receptor main-protease, whereas binding energy of curcumin (<a>-38.84</a> kcal/mol) had greater than hydroxychloroquine<a> (-35.87</a> kcal/mol) in case of S1 receptor binding domain. Therefore, this study suggested that the curcumin could be used as combination therapy along with hydroxychloroquine for disrupting the stability of SARS-CoV2 receptor proteins

Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Vol 20 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

scholarly journals Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2

In Vivo ◽  
2020 ◽  
Vol 34 (5) ◽  
pp. 3023-3026 ◽  
Author(s):  
STEVEN LEHRER ◽  
PETER H. RHEINSTEIN
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain

scholarly journals Neutralization of SARS‐CoV‐2 requires antibodies against conformational receptor‐binding domain epitopes

Allergy ◽  
2021 ◽  
Author(s):  
Pia Gattinger ◽  
Katarzyna Niespodziana ◽  
Karin Stiasny ◽  
Sabina Sahanic ◽  
Inna Tulaeva ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain
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