Sensing the interactions between carbohydrate-binding agents and N-linked glycans of SARS-CoV-2 spike glycoprotein using molecular docking and simulation studies. Issue 9 (23rd May 2022)

• Record Type: Journal Article
• Authors: Lokhande, Kiran Bharat; Apte, Girish R.; Shrivastava, Ashish; Singh, Ashutosh; Pal, Jayanta K.; , K. Venkateswara Swamy; Gupta, Rajesh Kumar
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 9(2022)
• Page Start: 3880
• Page End: 3898
• Publication Date: 2022-05-23
• Subjects: Lectin -- SARS-CoV-2 -- spike glycoprotein -- molecular docking and MD simulation -- Pradimicin-A; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2020.1851303
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: 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