SARS CoV-2 spike protein variants exploit DC-SIGN/DC-SIGNR receptor for evolution and severity: an in-silico insight

Jyoti Gupta; Md Zubbair Malik; Maya Chaturvedi; Mohit Mishra; Surbhi Kriti Mishra; Abhinav Grover; Ashwini Kumar Ray; Rupesh Chaturvedi

doi:10.1007/s13337-023-00820-3

SARS CoV-2 spike protein variants exploit DC-SIGN/DC-SIGNR receptor for evolution and severity: an in-silico insight

Virusdisease. 2023 May 24;34(2):1-19. doi: 10.1007/s13337-023-00820-3. Online ahead of print.

Authors

Jyoti Gupta¹, Md Zubbair Malik^{1

2}, Maya Chaturvedi¹, Mohit Mishra¹, Surbhi Kriti Mishra³, Abhinav Grover¹, Ashwini Kumar Ray⁴, Rupesh Chaturvedi^{1

5

6}

Affiliations

¹ New Delhi, 110067 India School of Biotechnology, Jawaharlal Nehru University.
² Dasman, 15462 Kuwait Department of Genetics and Bioinformatics, Dasman Diabetes Institute.
³ New Delhi, 110067 India School of Life Sciences, Jawaharlal Nehru University.
⁴ New Delhi, 11007 India Department of Environmental Studies, University of Delhi.
⁵ New Delhi, 110067 India Special Center for Systems Medicine, Jawaharlal Nehru University.
⁶ New Delhi, 110067 India Nanofludiks Research Pvt. Ltd., JNU-Atal Incubation Center, Jawaharlal Nehru University.

PMID: 37363363
PMCID: PMC10206574 (available on 2024-06-01)
DOI: 10.1007/s13337-023-00820-3

Abstract

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is related with the COVID-19 pandemic. Recent spike protein variations have had an effect on the transmission of the virus. In addition to ACE-2, spike proteins can employ DC-SIGN and its analogous receptor, DC-SIGNR, for host evasion. Spike variations in the DC-SIGN interaction region and role of DC-SIGN in immune evasion have not been well defined. To understand the spike protein variations and their binding mode, phylogenetic analysis of the complete GISAID (Global Initiative for Sharing Avian Influenza Data) data of the SARS-CoV-2 spike protein was considered. In addition, an in silico knockout network evaluation of the SARS-CoV-2 single-cell transcriptome was conducted to determine the key role of DC-SIGN/R in immunological dysregulation. Within the DC-SIGN-interacting region of the SARS-CoV spike protein, the spike protein of SARS-CoV-2 displayed remarkable similarity to the SARS-CoV spike protein. Surprisingly, the phylogenetic analysis revealed that the SARS-CoV-2's spike exhibited significantly diverse variants in the DC-SIGN interaction domain, which altered the frequency of these variants. The variation within the DC-SIGN-interacting domain of spike proteins affected the binding of a limited number of variants with DC-SIGN and DC-SIGNR and affected their evolution. MMGBSA binding free energies evaluation differed for variants from those of the wild type, suggesting the influence of substitution mutations on the interaction pattern. In silico knockout network analysis of the single-cell transcriptome of Bronchoalveolar Lavage and peripheral blood mononuclear cells revealed that SARS-CoV-2 altered DC-SIGN/R signaling. Early surveillance of diverse SARS-CoV-2 strains could preclude a worsening of the pandemic and facilitate the development of an optimum vaccine against variations. The spike Receptor Binding Domain genetic variants are thought to boost SARS CoV-2 immune evasion, resulting in its higher longevity.

Supplementary information: The online version contains supplementary material available at 10.1007/s13337-023-00820-3.

Keywords: DC-SIGN; DC-SIGN interacting region; DC-SIGN signalosome; DC-SIGNR; Immune dysregulation in silico; MMGBSA; Mapiya; SARS COV-2; Single cell transcriptome; Spike protein variant.

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