Structural Evolution of Delta Lineage of SARS-CoV-2

Overview

Journal Int J Biol Macromol

Publisher Elsevier

Date 2022 Nov 26

PMID 36435470

Authors

Mohammad Mahmoudi Gomari

Parastoo Tarighi

Edris Choupani

Shadi Abkhiz

Masoud Mohamadzadeh

Neda Rostami

Esmaeil Sadroddiny

Soukayna Baammi

Vladimir N Uversky

Nikolay V Dokholyan

Affiliations

Soon will be listed here.

Abstract

One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein. Given that Spike is the main target of common treatments of COVID-19, mutations occurring at this virulent factor can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, being characterized by many Spike mutations inside and outside of its receptor-binding domain (RBD), shows high infectivity and relative resistance to existing cures. Here, utilizing a wide range of computational biology approaches, such as immunoinformatics, molecular dynamics (MD), analysis of intrinsically disordered regions (IDRs), protein-protein interaction analyses, residue scanning, and free energy calculations, we examine the structural and biological attributes of the B.1.617.2 Spike protein. Furthermore, the antibody design protocol of Rosetta was implemented for evaluation the stability and affinity improvement of the Bamlanivimab (LY-CoV55) antibody, which is not capable of interactions with the B.1.617.2 Spike. We observed that the detected mutations in the Spike of the B1.617.2 variant of concern can cause extensive structural changes compatible with the described variation in immunogenicity, secondary and tertiary structure, oligomerization potency, Furin cleavability, and drug targetability. Compared to the Spike of Wuhan lineage, the B.1.617.2 Spike is more stable and binds to the Angiotensin-converting enzyme 2 (ACE2) with higher affinity.

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References

Taghizadeh M, Goliaei B, Madadkar-Sobhani A . Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study. Iran J Biotechnol. 2017; 14(2):1-12. PMC: 5435026. DOI: 10.15171/ijb.1419. View

Domingo E, Escarmis C, Lazaro E, Manrubia S . Quasispecies dynamics and RNA virus extinction. Virus Res. 2005; 107(2):129-39. DOI: 10.1016/j.virusres.2004.11.003. View

Kalsoom F, Sajjad-Ur-Rahman , Mahmood M, Zahoor T . Association of Interleukin-1B gene Polymorphism with infected Dyspeptic Gastric Diseases and Healthy Population. Pak J Med Sci. 2020; 36(4):825-830. PMC: 7260888. DOI: 10.12669/pjms.36.4.1883. View

Yamauchi M, Mori Y, Okumura H . Molecular simulations by generalized-ensemble algorithms in isothermal-isobaric ensemble. Biophys Rev. 2019; 11(3):457-469. PMC: 6557965. DOI: 10.1007/s12551-019-00537-y. View

Gromiha M, Selvaraj S . Inter-residue interactions in protein folding and stability. Prog Biophys Mol Biol. 2004; 86(2):235-77. DOI: 10.1016/j.pbiomolbio.2003.09.003. View

Gomari M, Rostami N, Omidi-Ardali H, Arab S . Insight into molecular characteristics of SARS-CoV-2 spike protein following D614G point mutation, a molecular dynamics study. J Biomol Struct Dyn. 2021; 40(12):5634-5642. PMC: 7832383. DOI: 10.1080/07391102.2021.1872418. View

Rostami N, Choupani E, Hernandez Y, Arab S, Jazayeri S, Gomari M . SARS-CoV-2 spike evolutionary behaviors; simulation of N501Y mutation outcomes in terms of immunogenicity and structural characteristic. J Cell Biochem. 2021; 123(2):417-430. PMC: 8657535. DOI: 10.1002/jcb.30181. View

van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark A, Berendsen H . GROMACS: fast, flexible, and free. J Comput Chem. 2005; 26(16):1701-18. DOI: 10.1002/jcc.20291. View

Gupta N, Kaur H, Yadav P, Mukhopadhyay L, Sahay R, Kumar A . Clinical Characterization and Genomic Analysis of Samples from COVID-19 Breakthrough Infections during the Second Wave among the Various States of India. Viruses. 2021; 13(9). PMC: 8472862. DOI: 10.3390/v13091782. View

10.

Wall E, Wu M, Harvey R, Kelly G, Warchal S, Sawyer C . Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet. 2021; 397(10292):2331-2333. PMC: 8175044. DOI: 10.1016/S0140-6736(21)01290-3. View

11.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

12.

Plante J, Liu Y, Liu J, Xia H, Johnson B, Lokugamage K . Spike mutation D614G alters SARS-CoV-2 fitness. Nature. 2020; 592(7852):116-121. PMC: 8158177. DOI: 10.1038/s41586-020-2895-3. View

13.

Gomari M, Saraygord-Afshari N, Farsimadan M, Rostami N, Aghamiri S, Farajollahi M . Opportunities and challenges of the tag-assisted protein purification techniques: Applications in the pharmaceutical industry. Biotechnol Adv. 2020; 45:107653. DOI: 10.1016/j.biotechadv.2020.107653. View

14.

Webb B, Sali A . Comparative Protein Structure Modeling Using MODELLER. Curr Protoc Bioinformatics. 2016; 54:5.6.1-5.6.37. PMC: 5031415. DOI: 10.1002/cpbi.3. View

15.

Muecksch F, Weisblum Y, Barnes C, Schmidt F, Schaefer-Babajew D, Wang Z . Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. Immunity. 2021; 54(8):1853-1868.e7. PMC: 8323339. DOI: 10.1016/j.immuni.2021.07.008. View

16.

Quaglia F, Salladini E, Carraro M, Minervini G, Tosatto S, Le Mercier P . SARS-CoV-2 variants preferentially emerge at intrinsically disordered protein sites helping immune evasion. FEBS J. 2022; 289(14):4240-4250. PMC: 9542094. DOI: 10.1111/febs.16379. View

17.

Chen J, Zaer S, Drori P, Zamel J, Joron K, Kalisman N . The structural heterogeneity of α-synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds. Structure. 2021; 29(9):1048-1064.e6. PMC: 8419013. DOI: 10.1016/j.str.2021.05.002. View

18.

Rajani H, Shahidi S, Gomari M . Protein and Antibody Engineering: Suppressing Degranulation of the Mast Cells and Type I Hypersensitivity Reaction. Curr Protein Pept Sci. 2020; 21(8):831-841. DOI: 10.2174/1389203721666200511094717. View

19.

Tam B, Sinha S, Wang S . Combining Ramachandran plot and molecular dynamics simulation for structural-based variant classification: Using variants as model. Comput Struct Biotechnol J. 2020; 18:4033-4039. PMC: 7744649. DOI: 10.1016/j.csbj.2020.11.041. View

20.

Smith E, Denison M . Coronaviruses as DNA wannabes: a new model for the regulation of RNA virus replication fidelity. PLoS Pathog. 2013; 9(12):e1003760. PMC: 3857799. DOI: 10.1371/journal.ppat.1003760. View