A Comprehensive Review about the Molecular Structure of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Insights into Natural Products against COVID-19

Abstract

In 2019, the world suffered from the emergence of COVID-19 infection, one of the most difficult pandemics in recent history. Millions of confirmed deaths from this pandemic have been reported worldwide. This disaster was caused by SARS-CoV-2, which is the last discovered member of the family of Coronaviridae. Various studies have shown that natural compounds have effective antiviral properties against coronaviruses by inhibiting multiple viral targets, including spike proteins and viral enzymes. This review presents the classification and a detailed explanation of the SARS-CoV-2 molecular characteristics and structure-function relationships. We present all currently available crystal structures of different SARS-CoV-2 proteins and emphasized on the crystal structure of different virus proteins and the binding modes of their ligands. This review also discusses the various therapeutic approaches for COVID-19 treatment and available vaccinations. In addition, we highlight and compare the existing data about natural compounds extracted from algae, fungi, plants, and scorpion venom that were used as antiviral agents against SARS-CoV-2 infection. Moreover, we discuss the repurposing of select approved therapeutic agents that have been used in the treatment of other viruses.

Keywords: COVID-19; SARS-CoV-2; antioxidants; antivirals; coronavirus; molecular structure; natural products; therapeutic approach; vaccines; virus detection; virus lifecycle.

Figure 1

Taxonomy of human coronaviruses.

Figure 2

(A) 3D graphical presentation of the structure of SARS-CoV-2 and human host cell receptors. (B) SARS-CoV-2 genome encodes for 16 nonstructural proteins (nsp), four structural proteins S, M, E, and N, and accessory proteins. A cartoon figure of the SARS-CoV-2 S protein that contains the two subunits: S1 and S2, where S1 composed of: SP (signal peptide); NTD (N-terminal domain), and CTD (C-terminal domain), while S2 composed of FP (fusion peptide), HR1 (heptad repeat 1), HR2 (heptad repeat 2), TM (transmembrane), and CP (cytoplasmic). There are two cleavage sites at S protein denoted as yellow arrows (S1/S2) and (S2′).

Figure 3

The binding interactions (in black) between N3 inhibitor (in green) and the key residues (in mustard yellow) of the active site in the main protease (Mpro) of SARS-CoV-2 (PDB:6lu7). The inhibitor is divided into 5 parts (P1, P1′, P2, P3, P4, and P5).

Figure 4

The binding interactions (black-dashed lines) between baicalein (green sticks) and the surrounding key amino acid residues (mustard yellow) of the active site in the main protease (Mpro) of SARS-CoV-2 (PDB: 6M2N).

Figure 5

Ribbon representation of Papain-like protease of SARS-CoV-2. (a) Ribbon representation of the structure of Papain-like protease of SARS-CoV-2 (PDB:7CMD) in its open conformation after removal of the ligand. It illustrates the four subdomains of the enzyme: N-terminal ubiquitin-like domain (Ubl, β1-3), α-helical Thumb domain (α2-7), β-stranded Finger domain (β4-7), and Palm domain (β8-13). Β-sheets are colored in yellow, while α-helices are colored in red. (b) Ribbon representation of liganded Papain-like protease of SARS-CoV-2 (PDB: 7CMD) with GRL0617 and its interaction with the receptor.

Figure 6

Overlay of ribbon representations of S-glycoprotein of SARS-CoV-2 in open conformation (in purple, PDB: 6vyb) and in closed conformation (in orange, PDB: 6vxx).

Figure 7

Ribbon representation of RdRp of SARS-CoV-2 (PDB code: 6yyt) which shows the active site of the enzyme (a) and illustrates the various domains of the enzyme (b). The RdRp structure consists of three subunits (nsp12, nsp8, and nsp7). The RdRp domain is fashioned into three subdomains (palm, fingers, and thumb subdomains). The nsp12 is mainly forms the active site of RdRb and comprised three domains (INRAN domain, C-terminal domain, and interface domain). The nsp8 and nsp7 subunits are binding to the fingers and thumb subdomains.

Figure 8

(a) Ribbon representation of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (PDB: 6M3M) which shows four monomers in an asymmetric unit, each colored in different color. (b) illustrates the four monomers superimposed on each other and shows the sandwich effect of two loop regions on the β-sheet core.