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Here, we compared a variety of replication features of SARS-CoV-2 and SARS-CoV and analysed the cytopathology caused by the two closely related viruses in the commonly used Vero E6 cell line. Compared to SARS-CoV, SARS-CoV-2 generated higher levels of intracellular viral RNA, but strikingly about 50-fold less infectious viral progeny was recovered from the culture medium. Immunofluorescence microscopy of SARS-CoV-2-infected cells established extensive cross-reactivity of antisera previously raised against a variety of non-structural proteins, membrane and nucleocapsid protein of SARS-CoV. Electron microscopy revealed that the ultrastructural changes induced by the two SARS viruses are very similar and occur within comparable time frames after infection. Furthermore, we determined that the sensitivity of the two viruses to three established inhibitors of coronavirus replication (remdesivir, alisporivir and chloroquine) is very similar, but that SARS-CoV-2 infection was substantially more sensitive to pre-treatment of cells with pegylated interferon alpha. An important difference between the two viruses is the fact that \u2013 upon passaging in Vero E6 cells \u2013 SARS-CoV-2 apparently is under strong selection pressure to acquire adaptive mutations in its spike protein gene. These mutations change or delete a putative furin-like cleavage site in the region connecting the S1 and S2 domains and result in a very prominent phenotypic change in plaque assays.<\/jats:p>","DOI":"10.1099\/jgv.0.001453","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T11:14:40Z","timestamp":1592824480000},"page":"925-940","source":"Crossref","is-referenced-by-count":559,"title":["SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology"],"prefix":"10.1099","volume":"101","author":[{"given":"Natacha S.","family":"Ogando","sequence":"first","affiliation":[{"name":"Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-7548","authenticated-orcid":false,"given":"Tim J.","family":"Dalebout","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessika C.","family":"Zevenhoven-Dobbe","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-6729","authenticated-orcid":false,"given":"Ronald W.A.L.","family":"Limpens","sequence":"additional","affiliation":[{"name":"Section Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2846-6729","authenticated-orcid":false,"given":"Leon","family":"Caly","sequence":"additional","affiliation":[{"name":"Virus Identification Laboratory, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Druce","sequence":"additional","affiliation":[{"name":"Virus Identification Laboratory, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutte J. 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