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

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

  • Sci Rep. 2023 Nov 17;13(1):20178. doi: 10.1038/s41598-023-47511-z.
Lee-Chin Chan # 1 2,  Aini Syahida Mat Yassim # 3 4 5,  Abdullah Al Hadi Ahmad Fuaad 6,  Thean Chor Leow 7 8 9,  Suriana Sabri 7 8,  Radin Shafierul Radin Yahaya 7,  Awang Muhammad Sagaf Abu Bakar 10
Affiliations

Affiliations

  • 1 Biovalence Sdn. Bhd., 22, Jalan SS 25/34, Taman Mayang, 47301, Petaling Jaya, Selangor, Malaysia.
  • 2 Biovalence Technologies Pte. Ltd., #06-307 The Plaza, 7500A Beach Road, Singapore, 199591, Singapore.
  • 3 Biovalence Sdn. Bhd., 22, Jalan SS 25/34, Taman Mayang, 47301, Petaling Jaya, Selangor, Malaysia. [email protected].
  • 4 Biovalence Technologies Pte. Ltd., #06-307 The Plaza, 7500A Beach Road, Singapore, 199591, Singapore. [email protected].
  • 5 School of Health Science, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. [email protected].
  • 6 Centre of Fundamental and Frontier Sciences in Self-Assembly (FSSA), Department of Chemistry, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
  • 7 Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
  • 8 Enzyme and Microbial Technology Research Center, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
  • 9 Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
  • 10 Jabatan Perkhidmatan Veterinar Sabah, Aras 3, Blok B, Wisma Pertanian Sabah, Jalan Tasik, Luyang (Off Jln Maktab Gaya), Beg Berkunci 2051, 88999, Kota Kinabalu, Sabah, Malaysia. [email protected].
  • # Contributed equally.
PMID: 37978223 DOI: 10.1038/s41598-023-47511-z
Abstract

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 3CLpro 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 RetroMAD1-3CLpro 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 RetroMAD1-3CLpro complex during simulations. In vitro experiments validated RetroMAD1's ability to inhibit 3CLpro 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.

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