Structural and functional insights into non-structural proteins of coronaviruses

Abstract

Coronaviruses (CoVs) are causing a number of human and animal diseases because of their zoonotic nature such as Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19). These viruses can infect respiratory, gastrointestinal, hepatic and central nervous systems of human, livestock, birds, bat, mouse, and many wild animals. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerging respiratory virus and is causing CoVID-19 with high morbidity and considerable mortality. All CoVs belong to the order Nidovirales, family Coronaviridae, are enveloped positive-sense RNA viruses, characterised by club-like spikes on their surfaces and large RNA genome with a distinctive replication strategy. Coronavirus have the largest RNA genomes (~26-32 kilobases) and their expansion was likely enabled by acquiring enzyme functions that counter the commonly high error frequency of viral RNA polymerases. Non-structural proteins (nsp) 7-16 are cleaved from two large replicase polyproteins and guide the replication and processing of coronavirus RNA. Coronavirus replicase has more or less universal activities, such as RNA polymerase (nsp 12) and helicase (nsp 13), as well as a variety of unusual or even special mRNA capping (nsp 14, nsp 16) and fidelity regulation (nsp 14) domains. Besides that, several smaller subunits (nsp 7- nsp 10) serve as essential cofactors for these enzymes and contribute to the emerging "nsp interactome." In spite of the significant progress in studying coronaviruses structural and functional properties, there is an urgent need to understand the coronaviruses evolutionary success that will be helpful to develop enhanced control strategies. Therefore, it is crucial to understand the structure, function, and interactions of coronaviruses RNA synthesizing machinery and their replication strategies.

Keywords: Control; Coronaviruses; Emerging; Human; Replication.

Fig. 1

SARS-CoV-2 nsp8 evolutionary changes in compared to other human coronaviruses. (a) Phylogenetic tree construction by the neighbour joining method was performed using MEGA X software, with bootstrap values being calculated from 1000 trees using amino acid sequences of nsp8 (b) Pairwise identity % plot of nsp8 CoVs amino acid sequences performed using SDT program, (c) 3D crystal structure of the nsp7- nsp8 complex of SARS-CoV-2 (PDB ID: 6YHU) and (d) Multiple amino acid sequence alignment for nsp8 of SARS-CoV-2 compared to other human coronaviruses.

Fig. 2

SARS-CoV-2 nsp13 evolutionary changes in compared to other human coronaviruses. (a) Phylogenetic tree construction by the neighbour joining method was performed using MEGA X software, with bootstrap values being calculated from 1000 trees using amino acid sequences of nsp13 (b) Pairwise identity % plot of nsp13 CoVs amino acid sequences performed using SDT program, (c) 3D crystal structure of the nsp13 of SARS-CoV-2 (PDB ID: 6JYT).

Fig. 3

SARS-CoV-2 nsp14 evolutionary changes in compared to other human coronaviruses. (a) Phylogenetic tree construction by the neighbour joining method was performed using MEGA X software, with bootstrap values being calculated from 1000 trees using amino acid sequences of nsp14 (b) Pairwise identity % plot of nsp14 CoVs amino acid sequences performed using SDT program, (c) 3D crystal structure of the nsp14- nsp10 complex of SARS-CoV-2(PDB ID: 5C8U).

Fig. 4

SARS-CoV-2 nsp15 evolutionary changes in compared to other human coronaviruses. (a) Phylogenetic tree construction by the neighbour joining method was performed using MEGA X software, with bootstrap values being calculated from 1000 trees using amino acid sequences of nsp15, (b) Pairwise identity % plot of nsp15 CoVs amino acid sequences performed using SDT program, (c) 3D crystal structure and (d) the multiple amino acid sequence alignment for of the nsp15 of SARS-CoV-2 (PDB ID: 6VWW) compared to other human coronaviruses.

Fig. 5

SARS-CoV-2 nsp16 evolutionary changes in compared to other human coronaviruses. (a) Phylogenetic tree construction by the neighbour joining method was performed using MEGA X software, with bootstrap values being calculated from 1000 trees using amino acid sequences of nsp16, (b) Pairwise identity % plot of nsp16 CoVs amino acid sequences performed using SDT program and (c) 3D crystal structure of the nsp16 of SARS-CoV-2 (PDB ID: 7BQ7).