{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:53:55Z","timestamp":1771037635644,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["Z201100006820128"],"award-info":[{"award-number":["Z201100006820128"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["Z211100002521017"],"award-info":[{"award-number":["Z211100002521017"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Science and technology plan","award":["Z201100006820128"],"award-info":[{"award-number":["Z201100006820128"]}]},{"name":"Beijing Science and technology plan","award":["Z211100002521017"],"award-info":[{"award-number":["Z211100002521017"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Viruses"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused huge social and economic distress. Given its rapid spread and the lack of specific treatment options, SARS-CoV-2 needs to be inactivated according to strict biosafety measures during laboratory diagnostics and vaccine development. The inactivation method for SARS-CoV-2 affects research related to the natural virus and its immune activity as an antigen in vaccines. In this study, we used size exclusion chromatography, western blotting, ELISA, an electron microscope, dynamic light scattering, circular dichroism, and surface plasmon resonance to evaluate the effects of four different chemical inactivation methods on the physical and biochemical characterization of SARS-CoV-2. Formaldehyde and \u03b2-propiolactone (BPL) treatment can completely inactivate the virus and have no significant effects on the morphology of the virus. None of the four tested inactivation methods affected the secondary structure of the virus, including the \u03b1-helix, antiparallel \u03b2-sheet, parallel \u03b2-sheet, \u03b2-turn, and random coil. However, formaldehyde and long-term BPL treatment (48 h) resulted in decreased viral S protein content and increased viral particle aggregation, respectively. The BPL treatment for 24 h can completely inactivate SARS-CoV-2 with the maximum retention of the morphology, physical properties, and the biochemical properties of the potential antigens of the virus. In summary, we have established a characterization system for the comprehensive evaluation of virus inactivation technology, which has important guiding significance for the development of vaccines against SARS-CoV-2 variants and research on natural SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/v14091938","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T03:55:38Z","timestamp":1662004538000},"page":"1938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Comparison of Physical and Biochemical Characterizations of SARS-CoV-2 Inactivated by Different Treatments"],"prefix":"10.3390","volume":"14","author":[{"given":"Shouzhi","family":"Yu","sequence":"first","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Wei","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyang","family":"Liang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenheng","family":"Ji","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Chang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siman","family":"Xie","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanli","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Biological Products Company Limited, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-4355","authenticated-orcid":false,"given":"Xiaoming","family":"Yang","sequence":"additional","affiliation":[{"name":"China National Biotec Group Company Limited, Beijing 100024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40794-022-00176-4","article-title":"Vaccines platforms and COVID-19: What you need to know","volume":"8","year":"2022","journal-title":"Trop. Dis. Travel Med. Vaccines"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Agrati, C., Carsetti, R., Bordoni, V., Sacchi, A., Quintarelli, C., Locatelli, F., Ippolito, G., and Capobianchi, M.R. (2022). The Immune Response as a Double-Edged Sword: The Lesson Learnt during the COVID-19 Pandemic. Immunology, Available online: https:\/\/onlinelibrary.wiley.com\/doi\/epdf\/10.1111\/imm.13564.","DOI":"10.1111\/imm.13564"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3390\/idr14030040","article-title":"Sarilumab Administration in COVID-19 Patients: Literature Review and Considerations","volume":"14","author":"Marino","year":"2022","journal-title":"Infect. Dis. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3892\/wasj.2020.64","article-title":"High-flow nasal cannula oxygenation and tocilizumab administration in patients critically ill with COVID-19: A report of three cases and a literature review","volume":"2","author":"Marino","year":"2020","journal-title":"World Acad. Sci. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Loveday, E.K., Hain, K.S., Kochetkova, I., Hedges, J.F., Robison, A., Snyder, D.T., Brumfield, S.K., Young, M.J., Jutila, M.A., and Chang, C.B. (2021). Effect of Inactivation Methods on SARS-CoV-2 Virion Protein and Structure. Viruses, 13.","DOI":"10.3390\/v13040562"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1093\/infdis\/jiaa507","article-title":"Methods of Inactivation of SARS-CoV-2 for Downstream Biological Assays","volume":"222","author":"Patterson","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.cell.2020.06.008","article-title":"Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2","volume":"182","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1001\/jama.2021.8565","article-title":"Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial","volume":"326","author":"Zhang","year":"2021","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"198555","DOI":"10.1016\/j.virusres.2021.198555","article-title":"Inactivation of SARS-CoV-2 by \u03b2-propiolactone causes aggregation of viral particles and loss of antigenic potential","volume":"305","author":"Gupta","year":"2021","journal-title":"Virus Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00430-021-00716-3","article-title":"Evaluation of stability and inactivation methods of SARS-CoV-2 in context of laboratory settings","volume":"210","author":"Widera","year":"2021","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.7150\/ijbs.52569","article-title":"Current advances in the development of SARS-CoV-2 vaccines","volume":"17","author":"Awadasseid","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.vaccine.2019.01.086","article-title":"Inactivated or damaged? Comparing the effect of inactivation methods on influenza virions to optimize vaccine production","volume":"37","author":"Signorazzi","year":"2019","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"001539","DOI":"10.1099\/jgv.0.001539","article-title":"Assessment of inactivation procedures for SARS-CoV-2","volume":"102","author":"Auerswald","year":"2021","journal-title":"J. Gen. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1128\/am.19.2.290-294.1970","article-title":"Effect of formalin, beta-propiolactone, merthiolate, and ultraviolet light upon influenza virus infectivity chicken cell agglutination, hemagglutination, and antigenicity","volume":"19","author":"Goldstein","year":"1970","journal-title":"Appl. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00038-17","DOI":"10.1128\/JVI.00038-17","article-title":"Beta-Propiolactone Inactivation of Coxsackievirus A16 Induces Structural Alteration and Surface Modification of Viral Capsids","volume":"91","author":"Fan","year":"2017","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.abc1932","article-title":"Development of an inactivated vaccine candidate for SARS-CoV-2","volume":"369","author":"Gao","year":"2020","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1080\/22221751.2020.1855945","article-title":"Biochemical and antigenic characterization of the structural proteins and their post-translational modifications in purified SARS-CoV-2 virions of an inactivated vaccine candidate","volume":"9","author":"Zhang","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, H., Xie, Z., Long, R., Fan, S., Li, H., He, Z., Xu, K., Liao, Y., Wang, L., and Zhang, Y. (2020). A valid protective immune response elicited in rhesus macaques by an inactivated vaccine is capable of defending against SARS-CoV-2 infection. bioRxiv, 2020.08.04.235747.","DOI":"10.1101\/2020.08.04.235747"},{"key":"ref_19","first-page":"3297","article-title":"Fast and reliable detection of SARS-CoV-2 antibodies based on surface plasmon resonance","volume":"13","author":"Basso","year":"2021","journal-title":"Anal. Methods Adv. Methods Appl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/elsc.202000106","article-title":"Purification and characterization of the receptor-binding domain of SARS-CoV-2 spike protein from Escherichia coli","volume":"21","author":"He","year":"2021","journal-title":"Eng. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.str.2020.10.001","article-title":"The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by Cryo-EM and Cryo-ET","volume":"28","author":"Liu","year":"2020","journal-title":"Structure"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1038\/s41467-020-18250-w","article-title":"Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B","volume":"11","author":"Wang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.cell.2020.09.018","article-title":"Molecular Architecture of the SARS-CoV-2 Virus","volume":"183","author":"Yao","year":"2020","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1001\/jama.2020.15543","article-title":"Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials","volume":"324","author":"Xia","year":"2020","journal-title":"JAMA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2305","DOI":"10.1002\/rmv.2305","article-title":"Safety and potency of BIV1-CovIran inactivated vaccine candidate for SARS-CoV-2: A preclinical study","volume":"32","author":"Abdoli","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1080\/22221751.2021.1971569","article-title":"Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies","volume":"10","author":"Kozlovskaya","year":"2021","journal-title":"Emerg. Microbes Infect."}],"updated-by":[{"DOI":"10.3390\/v15051035","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000}}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/9\/1938\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T13:54:04Z","timestamp":1754229244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/9\/1938"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,31]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["v14091938"],"URL":"https:\/\/doi.org\/10.3390\/v14091938","relation":{"correction":[{"id-type":"doi","id":"10.3390\/v15051035","asserted-by":"object"}]},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,31]]}}}