Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2

Tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein...

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Autor principal:	Penner Robert
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	mrna technology virus-vector virology vaccinology structural biology 92-08 92-10 92c05 Biotechnology TP248.13-248.65 Physics QC1-999
Acceso en línea:	https://doaj.org/article/d8f1b8f6200c425c8f397dbbc6e2091b
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spelling	oai:doaj.org-article:d8f1b8f6200c425c8f397dbbc6e2091b2021-12-05T14:10:44ZAntiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-22544-729710.1515/cmb-2020-0119https://doaj.org/article/d8f1b8f6200c425c8f397dbbc6e2091b2021-07-01T00:00:00Zhttps://doi.org/10.1515/cmb-2020-0119https://doaj.org/toc/2544-7297Tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargos that are resistant to viral mutation. This method is reviewed and reformulated in light of the recent proliferation of structural data on the SARS-CoV-2 spike glycoprotein and its mutations in multiple lineages. Key findings include: collections of mutagenic residues reoccur across strains, suggesting cooperative convergent evolution; most mutagenic residues do not participate in backbone hydrogen bonds; metastability of the glyco-protein limits the change of free energy through mutation thereby constraining selective pressure; and there are mRNA or virus-vector cargos targeting low free energy peptides proximal to conserved high free energy peptides providing specific recipes for vaccines with greater specificity than the full-spike approach. These results serve to limit peptides in the spike glycoprotein with high mutagenic potential and thereby provide a priori constraints on viral and attendant vaccine evolution. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are finally discussed.Penner RobertDe Gruyterarticlemrna technologyvirus-vectorvirologyvaccinologystructural biology92-0892-1092c05BiotechnologyTP248.13-248.65PhysicsQC1-999ENComputational and Mathematical Biophysics, Vol 9, Iss 1, Pp 81-89 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mrna technology virus-vector virology vaccinology structural biology 92-08 92-10 92c05 Biotechnology TP248.13-248.65 Physics QC1-999
spellingShingle	mrna technology virus-vector virology vaccinology structural biology 92-08 92-10 92c05 Biotechnology TP248.13-248.65 Physics QC1-999 Penner Robert Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
description	Tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargos that are resistant to viral mutation. This method is reviewed and reformulated in light of the recent proliferation of structural data on the SARS-CoV-2 spike glycoprotein and its mutations in multiple lineages. Key findings include: collections of mutagenic residues reoccur across strains, suggesting cooperative convergent evolution; most mutagenic residues do not participate in backbone hydrogen bonds; metastability of the glyco-protein limits the change of free energy through mutation thereby constraining selective pressure; and there are mRNA or virus-vector cargos targeting low free energy peptides proximal to conserved high free energy peptides providing specific recipes for vaccines with greater specificity than the full-spike approach. These results serve to limit peptides in the spike glycoprotein with high mutagenic potential and thereby provide a priori constraints on viral and attendant vaccine evolution. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are finally discussed.
format	article
author	Penner Robert
author_facet	Penner Robert
author_sort	Penner Robert
title	Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
title_short	Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
title_full	Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
title_fullStr	Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
title_full_unstemmed	Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2
title_sort	antiviral resistance against viral mutation: praxis and policy for sars-cov-2
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/d8f1b8f6200c425c8f397dbbc6e2091b
work_keys_str_mv	AT pennerrobert antiviralresistanceagainstviralmutationpraxisandpolicyforsarscov2
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Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2

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