دورية أكاديمية
أعرض في EDS

SARS-CoV-2 nsp14 Exoribonuclease Removes the Natural Antiviral 3'-Deoxy-3',4'-didehydro-cytidine Nucleotide from RNA.

التفاصيل البيبلوغرافية
العنوان: SARS-CoV-2 nsp14 Exoribonuclease Removes the Natural Antiviral 3'-Deoxy-3',4'-didehydro-cytidine Nucleotide from RNA.
المؤلفون: Moeller NH; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA., Passow KT; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA., Harki DA; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA., Aihara H; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
المصدر: Viruses [Viruses] 2022 Aug 16; Vol. 14 (8). Date of Electronic Publication: 2022 Aug 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: COVID-19* , Exoribonucleases*/metabolism, Antiviral Agents/pharmacology ; Cytidine/pharmacology ; Humans ; Mutation ; Nucleotides ; RNA ; RNA, Viral/metabolism ; RNA-Dependent RNA Polymerase/genetics ; SARS-CoV-2 ; Viral Nonstructural Proteins/metabolism ; Virus Replication
مستخلص: The on-going global pandemic of COVID-19 is caused by SARS-CoV-2, which features a proofreading mechanism to facilitate the replication of its large RNA genome. The 3'-to-5' exoribonuclease (ExoN) activity of SARS-CoV-2 non-structural protein 14 (nsp14) removes nucleotides misincorporated during RNA synthesis by the low-fidelity viral RNA-dependent RNA polymerase (RdRp) and thereby compromises the efficacy of antiviral nucleoside/nucleotide analogues. Here we show biochemically that SARS-CoV-2 nsp14 can excise the natural antiviral chain-terminating nucleotide, 3'-deoxy-3',4'-didehydro-cytidine 5'-monophosphate (ddhCMP), incorporated by RdRp at the 3' end of an RNA strand. Nsp14 ExoN processes an RNA strand terminated with ddhCMP more efficiently than that with a non-physiological chain terminator 3'-deoxy-cytidine monophosphate (3'-dCMP), whereas RdRp is more susceptible to chain termination by 3'-dCTP than ddhCTP. These results suggest that nsp14 ExoN could play a role in protecting SARS-CoV-2 from ddhCTP, which is produced as part of the innate immune response against viral infections, and that the SARS-CoV-2 enzymes may have adapted to minimize the antiviral effect of ddhCTP.
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معلومات مُعتمدة: P01 CA234228 United States CA NCI NIH HHS; R35 GM118047 United States GM NIGMS NIH HHS; U19 AI171954 United States AI NIAID NIH HHS; R35-GM118047 ; P01-CA234228 United States NH NIH HHS
فهرسة مساهمة: Keywords: RNA-dependent RNA polymerase; SARS-CoV-2; antiviral drug; chain terminator; ddhCTP; exoribonuclease; nsp14; nucleoside analogue; nucleotide; proofreading
المشرفين على المادة: 0 (Antiviral Agents)
0 (Nucleotides)
0 (RNA, Viral)
0 (Viral Nonstructural Proteins)
5CSZ8459RP (Cytidine)
63231-63-0 (RNA)
EC 2.1.1.56 (nsp14 protein, SARS coronavirus)
EC 2.7.7.48 (RNA-Dependent RNA Polymerase)
EC 3.1.- (Exoribonucleases)
تواريخ الأحداث: Date Created: 20220826 Date Completed: 20220829 Latest Revision: 20230603
رمز التحديث: 20230603
مُعرف محوري في PubMed: PMC9415739
DOI: 10.3390/v14081790
PMID: 36016411
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v14081790