Title:State-of-the-art Tools to Elucidate the Therapeutic Potential of TAT-peptide (TP)
Conjugated Repurposing Drug Against SARS-CoV-2 Spike Glycoproteins
Volume: 28
Issue: 46
Author(s): Mohammad Azam Ansari*, Mohammad N. Alomary, Qazi Mohammad Sajid Jamal, Yosif Almoshari, Ahmed Salawi, Suliman A. Almahmoud and Johra Khan
Affiliation:
- Department of Epidemic Disease Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal
University, Dammam, 31441, Saudi Arabia
Keywords:
SARS-CoV-2, TAT-peptide47-57 (GRKKRRQRRRP), molecular docking, repurposed drugs, acute respiratory disease, intracellular drug delivery.
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.
