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The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro.
Eberle, Raphael J; Olivier, Danilo S; Amaral, Marcos S; Gering, Ian; Willbold, Dieter; Arni, Raghuvir K; Coronado, Monika A.
  • Eberle RJ; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Olivier DS; Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße, 40225 Düsseldorf, Germany.
  • Amaral MS; Campus Cimba, Federal University of Tocantins, Araguaína, TO 77824-838, Brazil.
  • Gering I; Institute of Physics, Federal University of Mato Grosso do Sul, Campo Grande, MS 79070-900, Brazil.
  • Willbold D; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Arni RK; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Coronado MA; Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße, 40225 Düsseldorf, Germany.
Viruses ; 13(5)2021 05 10.
Article in English | MEDLINE | ID: covidwho-1290361
ABSTRACT
Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Quinacrine / Suramin / Coronavirus 3C Proteases Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13050873

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Quinacrine / Suramin / Coronavirus 3C Proteases Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13050873