Sensing the interactions between carbohydrate-binding agents and N-linked glycans of SARS-CoV-2 spike glycoprotein using molecular docking and simulation studies

J Biomol Struct Dyn. 2022 Jun;40(9):3880-3898. doi: 10.1080/07391102.2020.1851303. Epub 2020 Dec 9.


A recent surge in finding new candidate vaccines and potential antivirals to tackle atypical pneumonia triggered by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) needs new and unexplored approaches in solving this global pandemic. The homotrimeric transmembrane spike (S) glycoprotein of coronaviruses which facilitates virus entry into the host cells is covered with N-linked glycans having oligomannose and complex sugars. These glycans provide a unique opportunity for their targeting via carbohydrate-binding agents (CBAs) which have shown their antiviral potential against coronaviruses and enveloped viruses. However, CBA-ligand interaction is not fully explored in developing novel carbohydrate-binding-based antivirals due to associated unfavorable responses with CBAs. CBAs possess unique carbohydrate-binding specificity, therefore, CBAs like mannose-specific plant lectins/lectin-like mimic Pradimicin-A (PRM-A) can be used for targeting N-linked glycans of S glycoproteins. Here, we report studies on the binding and stability of lectins (NPA, UDA, GRFT, CV-N and wild-type and mutant BanLec) and PRM-A with the S glycoprotein glycans via docking and MD simulation. MM/GBSA calculations were also performed for docked complexes. Interestingly, stable BanLec mutant (H84T) also showed similar docking affinity and interactions as compared to wild-type BanLec, thus, confirming that uncoupling the mitogenic activity did not alter the lectin binding activity of BanLec. The stability of the docked complexes, i.e. PRM-A and lectins with SARS-CoV-2 S glycoprotein showed favorable intermolecular hydrogen-bond formation during the 100 ns MD simulation. Taking these together, our predicted in silico results will be helpful in the design and development of novel CBA-based antivirals for the SARS-CoV-2 neutralization.Communicated by Ramaswamy H. Sarma.

Keywords: Lectin; Pradimicin-A; SARS-CoV-2; molecular docking and MD simulation; spike glycoprotein.

MeSH terms

  • Antiviral Agents* / chemistry
  • COVID-19
  • Glycoproteins
  • Humans
  • Lectins
  • Molecular Docking Simulation
  • Polysaccharides / metabolism
  • SARS-CoV-2* / drug effects
  • Spike Glycoprotein, Coronavirus* / chemistry


  • Antiviral Agents
  • Glycoproteins
  • Lectins
  • Polysaccharides
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This work was supported by the Department of Science and Technology-Science and Engineering Research Board (DST-SERB), Government of India under the ECRA scheme [grant number ECR/2016/001187] and by Dr. D.Y. Patil Vidyapeeth, Pune [grant numbers DPU/106/18/2015, DPU/17/2016 (to Dr. Rajesh Kumar Gupta)]. Kiran Bharat Lokhande acknowledges the Indian Council of Medical Research (ICMR), New Delhi, for Senior Research Fellowship (Project ID: 2019-3458; file: ISRM/11(54)/2019).