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Current Pharmaceutical Design

Author(s): Mohammad Azam Ansari*, Mohammad N. Alomary, Qazi Mohammad Sajid Jamal, Yosif Almoshari, Ahmed Salawi, Suliman A. Almahmoud and Johra Khan

DOI: 10.2174/1381612829666221019144259

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State-of-the-art Tools to Elucidate the Therapeutic Potential of TAT-peptide (TP) Conjugated Repurposing Drug Against SARS-CoV-2 Spike Glycoproteins

Page: [3706 - 3719] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

Background: In late 2019, a highly infectious and pathogenic coronavirus was recognized as Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), which causes acute respiratory disease, threatening human health and public safety. A total of 448,327,303 documented cases and 6,028,576 deaths have been reported as of March 8th 2022. The COVID-19 vaccines currently undergoing clinical trials or already in use should provide at least some protection against SARS-CoV-2; however, the emergence of new variations as a result of mutations may lessen the effectiveness of the currently available vaccines. Since the efficacy of available drugs and vaccines against COVID-19 is notably lower, there is an urgent need to develop a potential drug to treat this deadly disease. The SARS-CoV-2 spike (SCoV-SG) is the foremost drug target among coronaviruses.

Objective: The major objectives of the current study are to conduct a molecular docking study investigation of TAT-peptide47-57(GRKKRRQRRRP)-conjugated remodified therapeutics such as ritonavir (RTV), lopinavir (LPV), favipiravir (FPV), remdesivir (RMV), hydroxychloroquine (HCQ), molnupiravir (MNV) and nirmatrelvir (NMV) with (SCoV-SG) structure.

Methods: Molecular docking analysis was performed to study the interaction of repurposed drugs and drugs conjugated with the TAT-peptide with target SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) using Auto- Dock. Further docking investigation was completed with PatchDock and was visualized by the discovery of the studio visualizer 2020.

Results: TAT-peptides are well-characterized immune enhancers that are used in intracellular drug delivery. The results of molecular docking analysis showed higher efficiency and significantly enhanced and improved interactions between TP-conjugated repurposed drugs and the target sites of the SCoV-SG structure.

Conclusion: The study concluded that TP-conjugated repurposed drugs may be effective in preventing COVID- 19, and therefore, in vitro, in vivo, and clinical trial studies are required in detail.

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