Structural biology of SARS-CoV-2: open the door for novel therapies

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of the pandemic disease COVID-19, which is so far without efficacious treatment. The discovery of therapy reagents for treating COVID-19 are urgently needed, and the structures of the potential drug-target proteins in the viral life cycle are particularly important. SARS-CoV-2, a member of the Orthocoronavirinae subfamily containing the largest RNA genome, encodes 29 proteins including nonstructural, structural and accessory proteins which are involved in viral adsorption, entry and uncoating, nucleic acid replication and transcription, assembly and release, etc. These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities. This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis, providing insights into the mechanisms underlying viral infection, prevention of infection, and treatment. Indeed, these studies open the door for COVID therapies, leading to ways to prevent and treat COVID-19, especially, treatment of the disease caused by the viral variants are imperative.

mRNA based vaccines provide broad protection against different SARS-CoV-2 variants of concern

“…The full-length SARS-CoV-2 spike protein encoded by the sequence-optimized mRNA is based on the original strain, and contains four mutations (K417N, E484K, N501Y, and D614G) found in the Beta variant [ 7 ]. The mRNA was obtained through in vitro transcription and then encapsulated in LNP through microfluidic system.…”

“…As of now, viruses belonging to lineages B.1.1.7 (Alpha), B.1.351 (Beta), B.1.1.28.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron) are classified as variants of concern (VOCs) based on their risk to public health [ 7 ]. The Beta, Delta, and the most recent Omicron strains contain several mutations in the spike gene to make these variants show high transmission and immune evasion [ 5 , 7–11 ]. Taking these into concerns, there is still a huge demand of COVID-19 vaccine globally to end the pandemic.…”

Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

“…Using the conserved sites of key SARS-CoV-2 virus proteins as targets for lowmolecular-weight antiviral drugs may be a more successful approach than a vaccine in both prevention and treatment [12]. One of the key interactions of a SARS-CoV-2 with a cell is the interaction between the receptor binding domain (RBD) of the S glycoprotein and Angiotensin-converting enzyme 2 (ACE2).…”

Pathogenic Mechanism and Multi-omics Analysis of Oral Manifestations in COVID-19

“…SARS-CoV-2 is a member of β-coronavirus genus ( 13 ). It contains four major structural proteins, including the spike (S) protein ( 14 ), which is an important virulence factor of SARS-CoV-2, mediating the entry of the virus into the host cells ( 4 ). Increasing evidence suggests that the occurrence and development of COVID-19 are related to the immune dysregulation caused by SARS-CoV-2 ( 15 , 16 ).…”