Host-cell recognition through GRP78 is enhanced in the new variants of SARS-CoV-2; in silico perspective

Host-cell recognition through GRP78 is enhanced in the new variants of SARS-CoV-2; in silico perspective | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Host-cell recognition through GRP78 is enhanced in the new variants of SARS-CoV-2; in silico perspective Abdo Elfiky, Ibrahim M Ibrahim, Alaa M Elgohary This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-189975/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 May, 2021 Read the published version in Biochemical and Biophysical Research Communications → Version 1 posted You are reading this latest preprint version Abstract New SARS-CoV-2 variants started in the UK and South Africa in December 2020 and currently spreading worldwide during the last few days. Additionally, another more recent variant sparked in Brazil (B.1.1.248 lineage) this month. The new variant 501.V2 (South African) bears three mutations in the receptor-binding domain (RBD) of the spike glycoprotein, K417N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage have 12 mutations. The N501Y mutation is found in South African and Brazilian variants and is also shared with the UK variant VOC-202012/01 (1). This mutation may affect the host-cell receptor ACE2 (angiotensin-converting enzyme 2) recognition (2). Despite its presence in the ACE2 binding surface, we showed that the N501Y mutant shows a remarkable increase in binding of the ACE2-RBD complex to the host-cell surface Glucose Regulated Protein 78 (CS-GRP78) (3). On the other hand, the E484K is found in the spike RBD's binding motif that we reported earlier to be recognized by cell-surface GRP78 (C480-C488 region of the spike) (4). In this study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wildtype and mutated (K417N, E484K, and N501Y) isoforms. Additionally, the CS-GRP78 association with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-RBD) is modeled at the presence of these mutant variants of the viral spike. Infectious Diseases SARS-CoV-2 new variants 501.V2 B.1.1.248 lineage computational biophysics GRP78 Spike RBD Figures Figure 1 Full Text Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF. Cite Share Download PDF Status: Published Journal Publication published 21 May, 2021 Read the published version in Biochemical and Biophysical Research Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-189975","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":9719220,"identity":"80ea208f-950a-4087-b05d-a239a9895fef","order_by":0,"name":"Abdo Elfiky","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYDACCQYDhg8MDDwQHhuRWhhnkKyFmQfOI0YL/+zmjY9t/tjJMLCfAbqw7DADP/8CApbcOVZsnNuWzMPAkwN04bnDDJIzHhCw5kaOmXRuwwEeBgkeA2betsMMBjcO4NchD9Ji8Qeq5S9Qiz0hLQYgLQxsUC2MIFv4G/BrMQT6xbAX6Bc2nrSCgz3n0nkkbhDwitzt5o0Pfvyxs+dnPwxklFnL8fcTcBgcgGIEpBbowgQitSAAP7G2jIJRMApGwUgBAMmoPGRTTpRXAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-4600-6240","institution":"Cairo University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Abdo","middleName":"","lastName":"Elfiky","suffix":""},{"id":9719221,"identity":"54e42fe6-8a3b-4252-bf31-42b90383157c","order_by":1,"name":"Ibrahim M Ibrahim","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ibrahim","middleName":"M","lastName":"Ibrahim","suffix":""},{"id":9719222,"identity":"99244b60-59fa-4591-bf93-b849030a8bd2","order_by":2,"name":"Alaa M Elgohary","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alaa","middleName":"M","lastName":"Elgohary","suffix":""}],"badges":[],"createdAt":"2021-01-30 08:45:33","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-189975/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-189975/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1016/j.bbrc.2021.05.058","type":"published","date":"2021-05-21T13:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":5793039,"identity":"06356b8f-0a8b-4dad-b550-400b2e0de8d8","added_by":"auto","created_at":"2021-02-09 18:57:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":645911,"visible":true,"origin":"","legend":"(A) The superposition of the docked complexes of GRP78 (green) to ACE2 (cyan)-SARS-CoV-2 Spike RBD (red) complex WT and Mutated (E484K). The enlarged panel on the right side shows the interacting residues in colored sticks in which WT RBD is blue, while the E484K mutant variant in magenta. (B)The per -residue RMSF calculated for the 25 ns period MDS on the SARS-CoV-2 spike RBD both WT (blue line) and mutated (orange line). Black dots represent the GRP78 binding region (C480-C488). The three mutants are shown in the RMSF graph (blue asterisk) and the structures (yellow and red sticks for WT and Mut, respectively).","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-189975/v1/19036c16dec8444df2b6e3fe.png"},{"id":13582710,"identity":"b245405b-b7cd-479d-acd7-d615f2dfcf6d","added_by":"auto","created_at":"2021-09-17 04:32:13","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":962217,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript25Jan2021.pdf","url":"https://assets-eu.researchsquare.com/files/rs-189975/v1_covered.pdf"},{"id":5793200,"identity":"c4b884a3-a29d-47ac-8a7c-a37ed1a140d7","added_by":"auto","created_at":"2021-02-09 19:00:46","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1308659,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript25Jan2021.pdf","url":"https://assets-eu.researchsquare.com/files/rs-189975/v1_stamped.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eHost-cell recognition through GRP78 is enhanced in the new variants of SARS-CoV-2; in silico perspective\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and \u003ca href='/article/rs-189975/latest.pdf' target='_blank'\u003e accessed as a PDF.\u003c/a\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"Cairo University","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"SARS-CoV-2 new variants, 501.V2, B.1.1.248 lineage, computational biophysics, GRP78, Spike RBD","lastPublishedDoi":"10.21203/rs.3.rs-189975/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-189975/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNew SARS-CoV-2 variants started in the UK and South Africa in December 2020 and currently spreading worldwide during the last few days. Additionally, another more recent variant sparked in Brazil (B.1.1.248 lineage) this month. The new variant 501.V2 (South African) bears three mutations in the receptor-binding domain (RBD) of the spike glycoprotein, K417N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage have 12 mutations. The N501Y mutation is found in South African and Brazilian variants and is also shared with the UK variant VOC-202012/01 (1). This mutation may affect the host-cell receptor ACE2 (angiotensin-converting enzyme 2) recognition (2). Despite its presence in the ACE2 binding surface, we showed that the N501Y mutant shows a remarkable increase in binding of the ACE2-RBD complex to the host-cell surface Glucose Regulated Protein 78 (CS-GRP78) (3). On the other hand, the E484K is found in the spike RBD's binding motif that we reported earlier to be recognized by cell-surface GRP78 (C480-C488 region of the spike) (4). In this study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wildtype and mutated (K417N, E484K, and N501Y) isoforms. Additionally, the CS-GRP78 association with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-RBD) is modeled at the presence of these mutant variants of the viral spike.\u003c/p\u003e","manuscriptTitle":"Host-cell recognition through GRP78 is enhanced in the new variants of SARS-CoV-2; in silico perspective","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-09 18:54:37","doi":"10.21203/rs.3.rs-189975/v1","editorialEvents":[{"type":"communityComments","content":2}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b3b3dad9-f633-4278-b19f-89689871a451","owner":[],"postedDate":"February 9th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":2155753,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2021-06-03T15:15:32+00:00","versionOfRecord":{"articleIdentity":"rs-189975","link":"https://doi.org/10.1016/j.bbrc.2021.05.058","journal":{"identity":"biochemical-and-biophysical-research-communications","isVorOnly":true,"title":"Biochemical and Biophysical Research Communications"},"publishedOn":"2021-05-21 13:00:00","publishedOnDateReadable":"May 21st, 2021"},"versionCreatedAt":"2021-02-09 18:54:37","video":"","vorDoi":"10.1016/j.bbrc.2021.05.058","vorDoiUrl":"https://doi.org/10.1016/j.bbrc.2021.05.058","workflowStages":[]},"version":"v1","identity":"rs-189975","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-189975","identity":"rs-189975","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}