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Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay.
Jang, Woo Dae; Jeon, Sangeun; Kim, Seungtaek; Lee, Sang Yup.
  • Jang WD; Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 four), KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
  • Jeon S; Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon 34141, Republic of Korea.
  • Kim S; Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Republic of Korea.
  • Lee SY; Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Republic of Korea; seungtaek.kim@ip-korea.org leesy@kaist.ac.kr.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Article in English | MEDLINE | ID: covidwho-1301228
ABSTRACT
The COVID-19 pandemic caused by SARS-CoV-2 is an unprecedentedly significant health threat, prompting the need for rapidly developing antiviral drugs for the treatment. Drug repurposing is currently one of the most tangible options for rapidly developing drugs for emerging and reemerging viruses. In general, drug repurposing starts with virtual screening of approved drugs employing various computational methods. However, the actual hit rate of virtual screening is very low, and most of the predicted compounds are false positives. Here, we developed a strategy for virtual screening with much reduced false positives through incorporating predocking filtering based on shape similarity and postdocking filtering based on interaction similarity. We applied this advanced virtual screening approach to repurpose 6,218 approved and clinical trial drugs for COVID-19. All 6,218 compounds were screened against main protease and RNA-dependent RNA polymerase of SARS-CoV-2, resulting in 15 and 23 potential repurposed drugs, respectively. Among them, seven compounds can inhibit SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, show anti-SARS-CoV-2 activities in human lung cells, Calu-3. Notably, the activity of omipalisib is 200-fold higher than that of remdesivir in Calu-3. Furthermore, three drug combinations, omipalisib/remdesivir, tipifarnib/omipalisib, and tipifarnib/remdesivir, show strong synergistic effects in inhibiting SARS-CoV-2. Such drug combination therapy improves antiviral efficacy in SARS-CoV-2 infection and reduces the risk of each drug's toxicity. The drug repurposing strategy reported here will be useful for rapidly developing drugs for treating COVID-19 and other viruses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Drug Repositioning / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Topics: Traditional medicine Limits: Animals / Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Drug Repositioning / COVID-19 Drug Treatment Type of study: Prognostic study / Randomized controlled trials Topics: Traditional medicine Limits: Animals / Humans Language: English Year: 2021 Document Type: Article