Mutational Landscape and Interaction of SARS-CoV-2 with Host Cellular Components

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid evolution has led to a global health crisis. Increasing mutations across the SARS-CoV-2 genome have severely impacted the development of effective therapeutics and vaccines to combat the virus. However, the new SARS-CoV-2 variants and their evolutionary characteristics are not fully understood. Host cellular components such as the ACE2 receptor, RNA-binding proteins (RBPs), microRNAs, small nuclear RNA (snRNA), 18s rRNA, and the 7SL RNA component of the signal recognition particle (SRP) interact with various structural and non-structural proteins of the SARS-CoV-2. Several of these viral proteins are currently being examined for designing antiviral therapeutics. In this review, we discuss current advances in our understanding of various host cellular components targeted by the virus during SARS-CoV-2 infection. We also summarize the mutations across the SARS-CoV-2 genome that directs the evolution of new viral strains. Considering coronaviruses are rapidly evolving in humans, this enables them to escape therapeutic therapies and vaccine-induced immunity. In order to understand the virus's evolution, it is essential to study its mutational patterns and their impact on host cellular machinery. Finally, we present a comprehensive survey of currently available databases and tools to study viral-host interactions that stand as crucial resources for developing novel therapeutic strategies for combating SARS-CoV-2 infection.

Keywords: RNA-binding proteins; SARS-CoV-2; host interaction; mutation; structural proteins; variants.

Figure 1

SARS-CoV-2s viral protein interactions with host cell structures and processes. (A) SARS-C0V-2 spike (S) protein interacts with host cell receptors ACE2 and TMPRSS2 for cellular entry. (B) Host cell membrane structure proteins interact with SARS-CoV-2 membrane (M) proteins for viral morphogenesis. (C) Host cell lipid processing channels such as ER, Golgi, and ERGIC interact with the SARS-CoV-2 Envelope (E) protein. (D) Host RNA processing components interact with SARS-CoV-2 N, E and Nsp (1,8,9,16), encoded by the SARS-CoV-2 genome. (E) Several structural and non-structural proteins in the SARS-Co-V-2 genome interact with components of the host innate immune system.

Figure 2

Mutations (synonymous, non-synonymous, deletion, and insertion) occurring across the SARS-CoV-2 genome. Only modifications that appear over 100 times in the dataset are in the figure. The frequency of each mutation by gene was calculated and displayed in the plot. Data for the plot can be found in the Supplementary Material of this publication. Genomic modifications and changes in the protein secondary structure and solvent accessibility of SARS-CoV-2 (COVID-19 virus) [144].