Network analysis and molecular mapping for SARS-CoV-2 to reveal drug targets and repurposing of clinically developed drugs

Virology. 2021 Mar;555:10-18. doi: 10.1016/j.virol.2020.12.006. Epub 2020 Dec 30.


Novel coronavirus (SARS-CoV-2), turned out to be a global pandemic with unstoppable morbidity and mortality rate. However, till date there is no effective treatment found against SARS-CoV-2. We report on the major in-depth molecular and docking analysis by using antiretroviral (Lopinavir and ritonavir), antimalarial (Hydroxychloroquine), antibiotics (Azithromycin), and dietary supplements (Vitamin C and E) to provide new insight into drug repurposing molecular events involved in SARS-CoV-2. We constructed three drug-target-pathways-disease networks to predict the targets and drugs interactions as well as important pathways involved in SARS-CoV-2. The results suggested that by using the combination of Lopinavir, Ritonavir along with Hydroxychloroquine and Vitamin C may turned out to be the effective line of treatment for SARS-CoV-2 as it shows the involvement of PARP-1, MAPK-8, EGFR, PRKCB, PTGS-2, and BCL-2. Gene ontology biological process analysis further confirmed multiple viral infection-related processes (P < 0.001), including viral life cycle, modulation by virus, C-C chemokine receptor activity, and platelet activation. KEGG pathway analysis involves multiple pathways (P < 0.05), including FoxO, GnRH, ErbB, Neurotrophin, Toll-like receptor, IL-17, TNF, Insulin, HIF-1, JAK-STAT, Estrogen, NF-kappa, Chemokine, VEGF, and Thyroid hormone signaling pathway in SARS-CoV-2. Docking study was carried out to predict the molecular mechanism Thus, the potential drug combinations could reduce viral infectivity, viral replication, and abnormal host inflammatory responses and may be useful for multi-target drugs against SARS-CoV-2.

Keywords: Drug repurposing; Molecular docking; Molecular mechanism; SARS–CoV–2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Ascorbic Acid / metabolism
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Drug Development
  • Drug Repositioning*
  • Drug Therapy, Combination
  • Humans
  • Hydroxychloroquine / metabolism
  • Hydroxychloroquine / pharmacology
  • Hydroxychloroquine / therapeutic use
  • Lopinavir / metabolism
  • Lopinavir / pharmacology
  • Lopinavir / therapeutic use
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • Ritonavir / metabolism
  • Ritonavir / pharmacology
  • Ritonavir / therapeutic use
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology
  • Signal Transduction
  • Virus Replication / drug effects


  • Antiviral Agents
  • Lopinavir
  • Hydroxychloroquine
  • Ritonavir
  • Ascorbic Acid