TAT-peptide conjugated repurposing drug against SARS-CoV-2 main protease (3CLpro): Potential therapeutic intervention to combat COVID-19
| Autor: | Mujeeb Khan, Mohammad N. Alomary, Syed Farooq Adil, Mohammad Azam Ansari, Ali H. Alharbi, Takshashila Tripathi, Mohammad A. Alzohairy, Ahmad Almatroudi, Qazi Mohammad Sajid Jamal, M. Shaheer Malik, Suriya Rehman |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
TAT-peptide repurposing drug General Chemical Engineering media_common.quotation_subject 02 engineering and technology Favipiravir Pharmacology 010402 general chemistry 01 natural sciences Article lcsh:Chemistry In vivo medicine Repurposing media_common SARS-CoV-2 Chemistry In silico COVID-19 Hydroxychloroquine Lopinavir General Chemistry 021001 nanoscience & nanotechnology 0104 chemical sciences Clinical trial lcsh:QD1-999 Molecular docking Ritonavir 0210 nano-technology 3CLpro main protease medicine.drug |
| Zdroj: | Arabian Journal of Chemistry Arabian Journal of Chemistry, Vol 13, Iss 11, Pp 8069-8079 (2020) |
| ISSN: | 1878-5352 |
| DOI: | 10.1016/j.arabjc.2020.09.037 |
| Popis: | The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Chinese city of Wuhan has caused around 906,092 deaths and 28,040,853 confirmed cases worldwide (https://covid19.who.int/, 11 September 2020). In a life-threatening situation, where there is no specific and licensed anti-COVID-19 vaccine or medicine available; the repurposed drug might act as a silver bullet. Currently, more than 211 vaccines, 80 antibodies, 31 antiviral drugs, 35 cell-based, 6 RNA-based and 131 other drugs are in clinical trials. It is therefore utter need of the hour to develop an effective drug that can be used for the treatment of COVID-19 before a vaccine can be developed. One of the best-characterized and attractive drug targets among coronaviruses is the main protease (3CLpro). Therefore, the current study focuses on the molecular docking analysis of TAT-peptide47–57 (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) with SARS-CoV-2 main protease (3CLpro) to discover potential efficacy of TAT-peptide (TP) - conjugated repurposing drugs against SARS-CoV-2. The molecular docking results validated that TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with the target SARS-CoV-2 main protease. In-silico approach employed in this study suggests that the combination of the drug with TP is an excelling alternative to develop a novel drug for the treatment of SARS-CoV-2 infected patients. The development of TP based delivery of repurposing drugs might be an excellent approach to enhance the efficacy of the existing drugs for the treatment of COVID-19. The predictions from the results obtained provide invaluable information that can be utilized for the choice of candidate drugs for in vitro, in vivo and clinical trials. The outcome from this work prove crucial for exploring and developing novel cost-effective and biocompatible TP conjugated anti-SARS-CoV-2 therapeutic agents in immediate future. |
| Databáze: | OpenAIRE |
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