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POSSIBLE PLATFORM TECHNOLOGY FOR A UNIVERSAL VACCINE THAT WORKS AGAINST ALL MUTANTS AND CAN BE EASILY TAILORED FOR ALL DIFFERENT VIRUSES.
Open access at https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.2548
IUBMB Life
. 2021 Aug 29. doi: 10.1002/iub.2548. Online ahead of print.
A decoy strategy to activate the immune system
Manisha S Deshpande*, Tanushree Banerjee
- PMID: 34455696
- DOI: 10.1002/iub.2548
Abstract
An approach comprising a novel fusion protein and inactivated virus, as a more efficacious vaccine against invading viruses is presented, using SARS-CoV-2 as a most prominent example. The fusion protein consists of the Hepatitis B surface antigen (HBsAg) conjugated to the N-terminal helix (NTH) of Angiotensin-Converting Enzyme 2 (ACE2), which is the receptor for SARS-CoV-2. For vaccination, this fusion protein is to be administered together with the whole killed virus. The NTH would bind to the Receptor Binding Domain (RBD) of the Spike protein of the killed virus. Due to HBsAg acting as a decoy, immune responses would be mounted. Neutralizing antibodies (NAbs) pre-existing in people already vaccinated with the recombinant Hepatitis B vaccine, fresh production of NAbs, and NAbs produced by memory B cells would bind to the HBsAg. This would lead to "presentation" of the killed virus to elements of the immune system at close range. Also, there would be enhanced opsonization and effective antigen presentation. This two-component vaccine could be a platform strategy, wherein HBsAg could be linked to the part of the cellular receptor that any new intractable virus binds to, and is administered together with whole inactivated virus. Now, the same fusion protein, administered by itself to persons with infection, would have therapeutic action, yet by harnessing elements of the immune system. NAbs would bind to the fusion protein as above, the NTH of which would bind to the RBDs of the infecting virus, which, in effect would be neutralized.
Keywords: HBsAg; N-terminal helix; SARS-CoV-2; decoy; fusion protein; immune activation.
© 2021 International Union of Biochemistry and Molecular Biology.
*Corresponding author
DISCLOSURE STATEMENT
Due to the benefit that could putatively arise from this work towards tackling the Covid-19 pandemic or other such viruses in the future, as a humanitarian gesture, no Intellectual Property Rights have been created for this study, and no further experimental work is being carried out. If any research laboratory across the world wishes to take up development of the proposed approach, the corresponding author may please be contacted.
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ADDITIONAL NOTE:- In place of the whole inactivated virus, a virus-like-particle (VLP) could be more effective.
Related:- Preprint DOI:- 10.31219/osf.io/y8gwz
https://osf.io/y8gwz/ (June 2021)
Proteins
2021 Aug 1. doi: 10.1002/prot.26198. Online ahead of print.
An In silico scientific basis for LL-37 as a therapeutic for Covid-19
Kiran Bharat Lokhande, Tanushree Banerjee, K Venkateswara Swamy, Payel Ghosh, Manisha Deshpande*
- PMID: 34333809
- DOI: 10.1002/prot.26198
Abstract
A multi-pronged approach with help in all forms possible is essential to completely overcome the Covid-19 pandemic. There is a requirement to research as many new and different types of approaches as possible to cater to the entire world population, complementing the vaccines with promising results. The need is also because SARS-CoV-2 has several unknown or variable facets which get revealed from time to time. In this work, in silico scientific findings are presented, which are indicative of the potential for the use of the LL-37 human anti-microbial peptide as a therapeutic against SARS-CoV-2. This indication is based on the high structural similarity of LL-37 to the N-terminal helix, with which the virus interacts, of the receptor for SARS-CoV-2, Angiotensin Converting Enzyme 2. Moreover, there is positive prediction of binding of LL-37 to the receptor-binding domain of SARS-CoV-2; the first study to have described this interaction. In silico data on the safety of LL-37 are also reported. As Vitamin D is known to upregulate the expression of LL-37, the vitamin is a candidate preventive molecule. This report provides the possible basis for why there is an inverse correlation between Vitamin D levels in the body and the severity of or susceptibility to Covid-19. With the scientific link put forth herein, Vitamin D could be used at an effective, medically prescribed, safe dose as a preventive. The information in this report would be valuable in bolstering the worldwide efforts to eliminate the pandemic as early as possible. This article is protected by copyright. All rights reserved.
Keywords: Covid-19; In silico Structural analysis; LL-37; Molecular Docking; Therapeutic; Vitamin D.
© 2021 Wiley Periodicals, Inc.
*Corresponding author
DISCLOSURE STATEMENT
Due to the benefit that could putatively arise from this work towards tackling the Covid-19 pandemic, as a humanitarian gesture, no Intellectual Property Rights have been created for this study, and no further experimental work is being carried out. If any research laboratory across the world wishes to take up development of the proposed approach, the corresponding author may please be contacted.
Wazoku Innocentive Innovation Award
Additional Information
A face mask that not only blocks but also entraps viruses, greatly enhancing protection and safety for the wearer. Low cost, feasible and safe technology.
Additional Option
The same mask can be modified to be able to also inactivate the entrapped viruses.
Hum Immunol
. 2010 Nov;71(11):1089-98. doi: 10.1016/j.humimm.2010.08.003. Epub 2010 Sep 17.
Immunologic properties of human dermal fibroblasts
Manisha Deshpande*, Shabari Tipnis, Prathibha Shetty, Deepa Ghosh, Chandra Viswanathan, Anish Sen Majumdar
- PMID: 20804801
- DOI: 10.1016/j.humimm.2010.08.003
Abstract
Human dermal fibroblasts are known not to express human leukocyte antigen (HLA)-DR message or protein in the absence of interferon (IFN)-γ. To use allogeneic dermal fibroblasts for cell therapy, as a revalidation, the cells at passage 12 were analyzed for HLA-DR mRNA and surface protein. Although no significant HLA-DR surface protein was found, HLA-DR mRNA expression was observed, without interferon-γ. At an early passage, although HLA-DR surface protein was not found, prominent expression of HLA-DR mRNA was observed without IFN-γ stimulation, which was not typical of dermal fibroblasts studied so far. Intracytoplasmic HLA-DR protein was also not detected, which suggests that the mRNA was not translated. There was no marked stimulation of T-cell proliferation by the fibroblasts in the absence or presence of IFN-γ. Interestingly, indoleamine dioxygenase, a molecule involved in immunosuppression, was also expressed in dermal fibroblasts in the absence of IFN-γ.
Copyright © 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
*Corresponding author
Biotechnol Prog
. Sep-Oct 2010;26(5):1424-30. doi: 10.1002/btpr.458.
A novel dermal tissue construct: development and in vitro characterization
Manisha S Deshpande*, Pushpa V Kuchroo
- PMID: 20549681
- DOI: 10.1002/btpr.458
Abstract
A dermal tissue construct composed of human dermal fibroblasts and a chitosan sponge has been developed, targeted towards the treatment of diabetic nonhealing ulcers. The construct has been designed in a way that the dermal fibroblasts are arranged as a three-dimensional sheet adhered entirely on one side of the chitosan sponge. This design would allow maximal diffusion of growth factors from the cells to the wound bed when the construct is applied on the wound with the cellular sheet side making contact with the wound bed. The diffusion of secreted growth factors would take place directly from cells to the wound bed without being impeded by a matrix. The cells are present at a high density in the dermal construct, which would aid in accelerated wound healing. The construct has a porous chitosan sponge base, which would allow gas exchange, and renders the dermal construct very flexible so that it would take the shape of the wound contours well, while having mechanical integrity. The viability of cells in the construct is greater than 90%. The dermal construct produces a high amount of vascular endothelial growth factor, from 42 ng to 31 ng in 24 h. The construct also produces high amounts of Interleukin-8 (IL-8), from 375 ng to 1065 ng in the first 24 h. Both VEGF and IL-8 have important roles in the healing of chronic diabetic ulcers.
© 2010 American Institute of Chemical Engineers
*Corresponding author
Diabetic Foot Ulcer - Tissue Engineering
Additional Information
Product research and development in Tissue Engineering/Regenerative Medicine: Development of a tissue engineered construct using chitosan sponge and dermal fibroblasts, for the treatment of diabetic non-healing ulcers, ‘from bench to clinic’. A pilot clinical trial was successfully conducted with positive safety and efficacy outcome. CTRI/2009/091/000513
Water, Environment, Sustainability
Additional Information
“Rainwater Management For A Resilient Mumbai and Drought Resistant Maharashtra Of The Future”, *Deshpande M, Joshi D, Kote A, Deshpande S, Kale V, Asalkar S, Thakur A. Scientific meeting with the office of the Additional Municipal Commissioner (Projects) at the Municipal Corporation of Greater Mumbai, Mumbai, 3rd Dec 2019.
“Rainwater Management For A Resilient Mumbai and Drought Resistant Maharashtra Of The Future”, *Deshpande M, Joshi D, Kote A, Deshpande S, Kale V, Asalkar S, Thakur A. Paper presented at the 6th India Water Week conference organised by the Ministry of Jal Shakti, Government of India, 24-28th September 2019 at Vigyan Bhawan, New Delhi.
*Corresponding author