TAT-peptide conjugated repurposing drug against SARS-CoV-2 main protease (3CLpro): Potential therapeutic intervention to combat COVID-19 |
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| Institution: | 1. Department of Epidemic Disease Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;2. Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah, Saudi Arabia;3. Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia;4. National Center for Biotechnology, Life Science and Environmental Research Institute, King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh, Saudi Arabia;5. Department of Neuroscience, Physiology, and Pharmacology, University College London, London, United Kingdom;6. Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia;7. Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, 21955 Makkah, Saudi Arabia |
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| Abstract: | 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. |
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| Keywords: | SARS-CoV-2 TAT-peptide COVID-19 In silico Molecular docking Repurposing drug |
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