Structural Characterization of SARS-CoV-2: Where We Are, and Where We Need to Be

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread in humans in almost every country, causing the disease COVID-19. Since the start of the COVID-19 pandemic, research efforts have been strongly directed towards obtaining a full understanding of the biology of the viral infection, in order to develop a vaccine and therapeutic approaches. In particular, structural studies have allowed to comprehend the molecular basis underlying the role of many of the SARS-CoV-2 proteins, and to make rapid progress towards treatment and preventive therapeutics. Despite the great advances that have been provided by these studies, many knowledge gaps on the biology and molecular basis of SARS-CoV-2 infection still remain. Filling these gaps will be the key to tackle this pandemic, through development of effective treatments and specific vaccination strategies.

An overview of basic molecular biology of SARS-CoV-2 and current COVID-19 prevention strategies

“…Many notable features of the SARS-CoV-2 and its full-length genome, based on experiment and comparison with SARS-CoV and related coronaviruses have been elucidated ( Andersen, 2020 ; Mariano et al, 2020 ; Wan et al, 2020 ; Zhou et al, 2020 ). The genome sequence of SARS-CoV-2 was found to have similar organization as that of CoVs ( Khailany and Ozaslan, 2020 ).…”

“…The four structural genes S, E, M, and N encodes the Spike protein (1273 amino acid), Envelope protein (75 amino acid), Membrane protein (222 amino acid), and Nucleocapsid phosphoprotein (419 amino acid) respectively. These four structural proteins in SARS-CoV-2 have been identified and characterized, where Envelope (E) and Membrane (M) protein are found to be involved in virus packing, and spike glycoprotein (S) in viral entry ( Mariano et al, 2020 ; Shang et al, 2020b ; Ye et al, 2020 ). The Nucleocapsid (N) protein is involved in RNA binding and packaging ( Mariano et al, 2020 ).…”

“…These four structural proteins in SARS-CoV-2 have been identified and characterized, where Envelope (E) and Membrane (M) protein are found to be involved in virus packing, and spike glycoprotein (S) in viral entry ( Mariano et al, 2020 ; Shang et al, 2020b ; Ye et al, 2020 ). The Nucleocapsid (N) protein is involved in RNA binding and packaging ( Mariano et al, 2020 ). Except spike protein, very limited structural information on the other structural proteins are available yet.…”

“…An identical leader sequence (protein of 180 amino acids) is carried by each mRNA ( Hoffmann et al, 2020 ; Kumar et al, 2020 ; Li, 2016 ). Orfs of SARS-CoV-2 have been validated and structural information of 9 accessory proteins have been discussed till date ( Khailany and Ozaslan, 2020 ; Mariano et al, 2020 ; Wu et al, 2020b ) ( Fig 2 A). SARS-CoV-2 encodes Orf10 in the genome terminal which was absent in SARS-CoVs and related strains, and a single Orf8 is found instead of Orf8a and Orf8b ( Nguyen et al, 2020 ).…”

Combined use of the hepatitis C drugs and amentoflavone could interfere with binding of the spike glycoprotein of SARS-CoV-2 to ACE2: the results of a molecular simulation study

“…Among them are the main protease (NSP5) and the papain-like protease (NSP3), which are responsible for the cleavage of the polyproteins into the mature NSP, the RNA-dependent RNA polymerase (NSP12), the helicase-triphosphatase (NSP13), the 3′-5′-exoribonuclease (NSP14), the RNA uridylate-specific endoribonuclease (NSP15), and N7- and 2′- O -methyltransferases (NSP10 and NSP16) (Arya et al, 2021 ). Due to the efforts of multiple research groups, the structural information on the SARS-CoV-2 proteins is rapidly increasing (Mariano et al, 2020 ). Currently, there are more than 1000 entries of SARS-CoV-2 proteins deposited in the protein data bank (PDB) (Berman et al, 2000 , http://www.rcsb.org/ ).…”