Common low complexity regions for SARS-CoV-2 and human proteomes as potential multidirectional risk factor in vaccine...

Area of Science:

• Virology
• Immunology
• Bioinformatics

Background:

• COVID-19 necessitates rapid development of effective countermeasures, requiring careful selection of viral targets (epitopes).
• Existing research on SARS-CoV-2 targets has focused on proteome-wide or phylogenetic analyses, neglecting viral protein low complexity regions (LCRs).
• Novel methods for comparing LCRs have recently been developed.

Purpose of the Study:

• To investigate the presence and significance of low complexity regions (LCRs) in SARS-CoV-2 proteins.
• To compare SARS-CoV-2 LCRs with human proteome sequences.
• To assess the potential impact of these LCRs on immune evasion and vaccine development.

Main Methods:

• Comparative analysis of SARS-CoV-2 proteome, specifically focusing on low complexity regions (LCRs).
• Utilized newly developed methods for comparing LCR fragments across different proteomes.
• Identified overlapping regions between viral LCRs and predicted T-cell and B-cell epitopes.

Main Results:

• Five low complexity regions (LCRs) were identified in three SARS-CoV-2 proteins (nsp3, S, and N) that show high similarity to human proteome regions.
• A significant number of predicted T-cell (21) and B-cell (27) epitopes overlap with these human-like LCRs.
• Replication proteins in the central viral RNA were found to lack LCRs.

Conclusions:

• The similarity of SARS-CoV-2 LCRs to human proteins may enable viral immune evasion.
• Vaccines targeting these LCRs could be ineffective or potentially trigger autoimmune responses.
• It is crucial to exclude these homologous LCRs when selecting epitopes for vaccines and antiviral drugs.