Structural and molecular perspectives of SARS-CoV-2

• Published in: Methods (San Diego, Calif.) Calif.), 2021-11, Vol.195, p.23-28
• Main Authors: Kumar, Swatantra, Saxena, Shailendra K.
• Format: Article
• Language: English
• Subjects: ACE2; Animals; Binding Sites - physiology; COVID-19; COVID-19 - epidemiology; COVID-19 - metabolism; Humans; Mpro; nsp10/nsp16 2′-O-methylase; Nucleocapsid; Protein Structure, Secondary; SARS-CoV-2; SARS-CoV-2 - chemistry; SARS-CoV-2 - metabolism; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - metabolism; Spike-glycoprotein; Virus Internalization; Virus Replication - physiology
• ISSN: 1046-2023; 1095-9130
• DOI: 10.1016/j.ymeth.2021.03.007

•Spike glycoprotein undergoes two conformational states i.e. receptor-inaccessible state and receptor-accessible state upon binding to ACE2.•S1 subunit involved in the attachment to the peptidase domain (PD) of the ACE2 receptor via RBD and S2 subunit involved in cell and viral membrane fusion.•SARS-CoV-2 and SARS-CoV RBDs use eight identical interacting residues for attachment to the ACE2 receptor.•Main protease (Mpro) doesn’t share cleavage sites with any human encoded proteases; therefore, it can be one of the best drug targets for combating CoVs. Recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transpired into pandemic coronavirus disease 2019 (COVID-19). SARS-CoV-2 has been rapidly transmitted across the globe within a short period of time, with more than 106 million cases and 2.3 million deaths. The continuous rise in worldwide cases of COVID-19, transmission dynamics of SARS-CoV-2 including re-infections and enormous case-fatality rates emphasizes the urgent need of potential preventive and therapeutic measures. The development of effective therapeutic and preventive measures relies on understanding the molecular and cellular mechanism of replication exhibited by SARS-CoV-2. The structure of SARS-CoV-2 is ranging from 90–120 nm that comprises surface viral proteins including spike, envelope, membrane which are attached in host lipid bilayer containing the helical nucleocapsid comprising viral RNA. Spike (S) glycoprotein initiates the attachment of SARS-CoV-2 with a widely expressed cellular receptor angiotensin-converting enzyme 2 (ACE2), and subsequent S glycoprotein priming via serine protease TMPRSS2. Prominently, comprehensive analysis of structural insights into the crucial SARS-CoV-2 proteins may lead us to design effective therapeutics molecules. The present article, emphasizes the molecular and structural perspective of SARS-CoV-2 including mechanistic insights in its replication.