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Synthetically recoded virus sCPD9 - A tool to accelerate SARS-CoV-2 research under biosafety level 2 conditions.
Kunec, Dusan; Osterrieder, Nikolaus; Trimpert, Jakob.
  • Kunec D; Institut für Virologie, Freie Universität Berlin, Berlin, Germany.
  • Osterrieder N; Institut für Virologie, Freie Universität Berlin, Berlin, Germany.
  • Trimpert J; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
Comput Struct Biotechnol J ; 20: 4376-4380, 2022.
Article in English | MEDLINE | ID: covidwho-2000365
ABSTRACT
Research with infectious SARS-CoV-2 is complicated because it must be conducted under biosafety level 3 (BSL-3) conditions. Recently, we constructed a live attenuated SARS-CoV-2 virus by rational design through partial recoding of the SARS-CoV-2 genome and showed that the attenuated virus, designated sCPD9, was highly attenuated in preclinical animal models. The recoded sequence was designed by codon pair deoptimization and is located at the distal end of gene ORF1ab. Codon pair deoptimization involves recoding of the viral sequence with underrepresented codon pairs but without altering the amino acid sequence of the encoded proteins. Thus, parental and attenuated viruses produce exactly the same proteins. In Germany, the live attenuated SARS-CoV-2 mutant sCPD9 was recently classified as a BSL-2 pathogen based on its genetic stability and strong attenuation in preclinical animal models. Despite its high attenuation in vivo, sCPD9 grows to high titers in common cell lines, making it suitable as substitute for virulent SARS-CoV-2 in many experimental setups. Consequently, sCPD9 can ease and accelerate SARS-CoV-2 research under BSL-2 conditions, particularly in experiments requiring replicating virus, such as diagnostics and development of antiviral drugs.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Comput Struct Biotechnol J Year: 2022 Document Type: Article Affiliation country: J.csbj.2022.08.027

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Comput Struct Biotechnol J Year: 2022 Document Type: Article Affiliation country: J.csbj.2022.08.027