Inhibition of SARS-CoV-2 3CL protease by the anti-viral chimeric protein RetroMAD1

COVID-19 results from SARS-CoV-2, which mutates frequently, challenging current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. This study explores the interaction between SARS-CoV-2 3CL pro and RetroMAD1, a well-characterized coronavirus protein and pote...

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Bibliographic Details
Published in:Scientific reports 2023-11, Vol.13 (1), p.20178-20178, Article 20178
Main Authors: Chan, Lee-Chin, Mat Yassim, Aini Syahida, Ahmad Fuaad, Abdullah Al Hadi, Leow, Thean Chor, Sabri, Suriana, Radin Yahaya, Radin Shafierul, Abu Bakar, Awang Muhammad Sagaf
Format: Article
Language:English
Subjects:
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Antiviral agents
Coronaviruses
COVID-19
Cytotoxicity
Drug development
Enzymatic activity
Humanities and Social Sciences
Hydrogen bonding
Molecular dynamics
multidisciplinary
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Therapeutic targets
Thermodynamics
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Summary:COVID-19 results from SARS-CoV-2, which mutates frequently, challenging current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. This study explores the interaction between SARS-CoV-2 3CL pro and RetroMAD1, a well-characterized coronavirus protein and potential drug target, using in-silico methods. The analysis through the HDOCK server showed stable complex formation with a binding energy of -12.3, the lowest among reference drugs. The RetroMAD1-3CL pro complex underwent a 100 ns molecular dynamics simulation (MDS) in an explicit solvation system, generating various trajectories, including RMSD, RMSF, hydrogen bonding, radius of gyration, and ligand binding energy. MDS results confirmed intact interactions within the RetroMAD1-3CL pro complex during simulations. In vitro experiments validated RetroMAD1's ability to inhibit 3CL pro enzyme activity and prevent SARS-CoV-2 infection in human bronchial cells. RetroMAD1 exhibited antiviral efficacy comparable to Remdesivir without cytotoxicity at effective concentrations. These results suggest RetroMAD1 as a potential drug candidate against SARS-CoV-2, warranting further in vivo and clinical studies to assess its efficiency.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-47511-z