Main protease inhibitors and drug surface hotspots for the treatment of COVID-19: A drug repurposing and molecular docking approach

Mahmudul Hasan, Md Sorwer Alam Parvez, Kazi Faizul Azim, Md Abdus Shukur Imran, Topu Raihan, Airin Gulshan, Samuel Muhit, Rubaiat Nazneen Akhand, Syed Sayeem Uddin Ahmed, Md Bashir Uddin

Research output: Contribution to journalArticlepeer-review


Here, drug repurposing and molecular docking were employed to screen approved MPP inhibitors and their derivatives to suggest a specific therapeutic agent for the treatment of COVID-19. The approved MPP inhibitors against HIV and HCV were prioritized, while RNA dependent RNA Polymerase (RdRp) inhibitor remdesivir including Favipiravir, alpha-ketoamide were studied as control groups. The target drug surface hotspot was also investigated through the molecular docking technique. Molecular dynamics was performed to determine the binding stability of docked complexes. Absorption, distribution, metabolism, and excretion analysis was conducted to understand the pharmacokinetics and drug-likeness of the screened MPP inhibitors. The results of the study revealed that Paritaprevir (−10.9 kcal/mol) and its analog (CID 131982844) (−16.3 kcal/mol) showed better binding affinity than the approved MPP inhibitors compared in this study, including remdesivir, Favipiravir, and alpha-ketoamide. A comparative study among the screened putative MPP inhibitors revealed that the amino acids T25, T26, H41, M49, L141, N142, G143, C145, H164, M165, E166, D187, R188, and Q189 are at potentially critical positions for being surface hotspots in the MPP of SARS-CoV-2. The top 5 predicted drugs (Paritaprevir, Glecaprevir, Nelfinavir, and Lopinavir) and the topmost analog showed conformational stability in the active site of the SARS-CoV-2 MP protein. The study also suggested that Paritaprevir and its analog (CID 131982844) might be effective against SARS-CoV-2. The current findings are limited to in silico analysis and lack in vivo efficacy testing; thus, we strongly recommend a quick assessment of Paritaprevir and its analog (CID 131982844) in a clinical trial.

Original languageEnglish (US)
Article number111742
JournalBiomedicine and Pharmacotherapy
StatePublished - Aug 2021
Externally publishedYes


  • COVID-19
  • Drug repurposing
  • Main protease protein (MPP) inhibitors
  • Molecular docking
  • SARS-CoV-2

ASJC Scopus subject areas

  • Pharmacology


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