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Pierce Into Structural Changes of Interactions Between Mutated Spike Glycoproteins and Ace2 to Evaluate Its Potential Biological and Therapeutic Consequences Publisher



Hashemi ZS1 ; Zarei M2 ; Mubarak SMH3 ; Hessami A4 ; Mardsoltani M5 ; Khalesi B6 ; Zakeri A7 ; Rahbar MR2 ; Jahangiri A8 ; Pourzardosht N9 ; Khalili S7
Authors
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Authors Affiliations
  1. 1. ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
  2. 2. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Department of Clinical Laboratory Science, Faculty of Pharmacy, University of Kufa, Najaf, Iraq
  4. 4. School of Pharmacy, Shiraz University of medical sciences, Shiraz, Iran
  5. 5. Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
  6. 6. Department of Research and Production of Poultry Viral Vaccine, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization, Karaj, Iran
  7. 7. Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran
  8. 8. Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
  9. 9. Biochemistry Department, Guilan University of Medical Sciences, Rasht, Iran

Source: International Journal of Peptide Research and Therapeutics Published:2022


Abstract

The structural consequences of ongoing mutations on the SARS-CoV-2 spike-protein remains to be fully elucidated. These mutations could change the binding affinity between the virus and its target cell. Moreover, obtaining new mutations would also change the therapeutic efficacy of the designed drug candidates. To evaluate these consequences, 3D structure of a mutant spike protein was predicted and checked for stability, cavity sites, and residue depth. The docking analyses were performed between the 3D model of the mutated spike protein and the ACE2 protein and an engineered therapeutic ACE2 against COVID-19. The obtained results revealed that the N501Y substitution has altered the interaction orientation, augmented the number of interface bonds, and increased the affinity against the ACE2. On the other hand, the P681H mutation contributed to the increased cavity size and relatively higher residue depth. The binding affinity between the engineered therapeutic ACE2 and the mutant spike was significantly higher with a distinguished binding orientation. It could be concluded that the mutant spike protein increased the affinity, preserved the location, changed the orientation, and altered the interface amino acids of its interaction with both the ACE2 and its therapeutic engineered version. The obtained results corroborate the more aggressive nature of mutated SARS-CoV-2 due to their higher binding affinity. Moreover, designed ACe2-baased therapeutics would be still highly effective against covid-19, which could be the result of conserved nature of cellular ACE2. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.
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