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Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs.
Neogi, Ujjwal; Hill, Kyle J; Ambikan, Anoop T; Heng, Xiao; Quinn, Thomas P; Byrareddy, Siddappa N; Sönnerborg, Anders; Sarafianos, Stefan G; Singh, Kamal.
  • Neogi U; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, 14186 Stockholm, Sweden.
  • Hill KJ; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
  • Ambikan AT; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
  • Heng X; Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
  • Quinn TP; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, 14186 Stockholm, Sweden.
  • Byrareddy SN; Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
  • Sönnerborg A; Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
  • Sarafianos SG; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Centre, Omaha, NE 68198, USA.
  • Singh K; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
Pathogens ; 9(5)2020 Apr 26.
Article in English | MEDLINE | ID: covidwho-1448915
ABSTRACT
Coronaviruses (CoVs) are positive-stranded RNA viruses that infect humans and animals. Infection by CoVs such as HCoV-229E, -NL63, -OC43 and -HKU1 leads to the common cold, short lasting rhinitis, cough, sore throat and fever. However, CoVs such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and the newest SARS-CoV-2 (the causative agent of COVID-19) lead to severe and deadly diseases with mortality rates ranging between ~1 to 35% depending on factors such as age and pre-existing conditions. Despite continuous global health threats to humans, there are no approved vaccines or drugs targeting human CoVs, and the recent outbreak of COVID-19 emphasizes an urgent need for therapeutic interventions. Using computational and bioinformatics tools, here we present the feasibility of reported broad-spectrum RNA polymerase inhibitors as anti- SARS-CoV-2 drugs targeting its main RNA polymerase, suggesting that investigational and approved nucleoside RNA polymerase inhibitors have potential as anti-SARS-CoV-2 drugs. However, we note that it is also possible for SARS-CoV-2 to evolve and acquire drug resistance mutations against these nucleoside inhibitors.
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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Year: 2020 Document Type: Article Affiliation country: Pathogens9050320

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Year: 2020 Document Type: Article Affiliation country: Pathogens9050320