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Evaluation of short peptide epitope regions covering mutations of SARS-CoV-2 receptor binding domain: An ELISA based serological test

AbstractSince the first discovery of COVID-19 in late 2019, several millions of people have beeninfected worldwide by the novel severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Towards the end of the following year new mutant variants started emerging,namely 20I/501Y.V1, VOC 202012/01, or B.1.1.7, 20H/501Y.V2 or B.1.351 P.1(descendant of B.1.1.28), which were firstly discovered in United Kingdom, SouthAfrica, and Brazil, respectively. These variants contain several mutations located in thedifferent part of the virus genome. In this work, we focus mainly on commonly sharedmutations in the receptor binding domain (RBD) of the spike protein, E484K and N501Y.There is some evidence indicating that these mutations could increase diseasetransmissibility between humans. Here, we explore a concept of employing a diagnostictool to evaluate the importance of these mutations using short peptide epitopes containingthe mutations. A naturally occurring biologically stable cyclic peptide, sunflower trypsininhibitor 1 (SFTI-1), was used as a molecular scaffold to graft the epitopes. The epitopeswere tested against five serum samples and by using an indirect enzyme-linkedimmunosorbent assay (ELISA) the strength and/or response of the antibody reactivitywas determined. Linear versions of the cyclic peptides and RBD, as well as a longer nativelinear peptide containing both regions of mutation sites were used as controls. Initialresults suggest that short epitopes are insufficient to trigger antibody reactivity and thatepitope regions selection plays an important role. However, the insight presented in thiswork provides substantial information for future development of pharmaceuticalapproaches in COVID-19 therapy.

Identiferoai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-449521
Date January 2021
CreatorsPersson, Jay
PublisherUppsala universitet, Institutionen för farmaceutisk biovetenskap
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeStudent thesis, info:eu-repo/semantics/bachelorThesis, text
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess

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