SARS coronavirus 2: from genome to infectome

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the group of Betacoronaviruses. The SARS-CoV-2 is closely related to SARS-CoV-1 and probably originated either from bats or pangolins. SARS-CoV-2 is an etiological agent of COVID-19, causing mild to severe respiratory disease which escalates to acute respiratory distress syndrome (ARDS) or multi-organ failure. The virus was first reported from the animal market in Hunan, Hubei province of China in the month of December, 2019, and was rapidly transmitted from animal to human and human-to-human. The human-to-human transmission can occur directly or via droplets generated during coughing and sneezing. Globally, around 53.9 million cases of COVID-19 have been registered with 1.31 million confirmed deaths. The people > 60 years, persons suffering from comorbid conditions and immunocompromised individuals are more susceptible to COVID-19 infection. The virus primarily targets the upper and the lower respiratory tract and quickly disseminates to other organs. SARS-CoV-2 dysregulates immune signaling pathways which generate cytokine storm and leads to the acute respiratory distress syndrome and other multisystemic disorders.

Keywords: ACE2 receptors; Acute respiratory distress syndrome (ARDS); COVID-19; Coronaviruses; SARS-CoV-2; Spike glycoprotein.

Fig. 1

The transmission cycle of SARS-CoV-2. The SARS-CoV-2 originated from bats and pangolins are presumed to be their intermediate amplifying hosts. The virus transmits from animal-to-human to human-to-human. The infected person transmits the virus through cough and sneeze. In the population, there are asymptomatic carrier which spread the virus without any signs or symptoms

Fig. 2

Schematic presentation of the SARS-CoV-2 genome Structure. SARS-CoV-2 has a spherical structure. The virus has an outer lipid envelope, covered with spike glycoprotein. The SARS-CoV-2 represents a typical Betacoronavirus genome organisation. The full-length RNA genome comprises of approximately 29,903 nucleotides and has a replicase complex (comprised of ORF1a and ORF1b) at the 5′UTR. The ORF1a encodes for nsp1–nsp10, while ORF1b encodes for nsp1–nsp16. Four genes that encode for the Structural proteins: Spike gene, Envelope gene, Membrane gene, Nucleocapsid gene and a poly (A) tail at the 3′UTR. The accessory genes are distributed in between the structural genes

Fig. 3

The SARS-CoV-2 replication and pathogenesis. a The SARS-CoV-2 infects upper and lower respiratory tract. b The virus replication from 1 to 12 has been described as, (1) The virus identifies the ACE-2 receptor. (2) The binding is initiated by the Spike (S) glycoprotein of SARS-CoV-2 by receptor binding domain (RBD) to the ACE-2 receptor binding motif (RBM). (3, 4) The virus-receptor internalization occurs and a membrane fusion is carried out by S2 subunit of S glycoprotein followed by the uncoating of +ssRNA inside cytoplasm. (5–7) The +ssRNA directly translate into non-structural proteins for initiating the viral replication through RNA-dependent RNA polymerase (RdRp/nsp12) and forms -ssRNA which act as template for synthesizing various copies of +ssRNA. (8–10) The +ssRNA along with the structural protein are trafficked to ER-Golgi complex for assembly and maturation. (11–12) The vesicles-encapsulated virion fuses with the cell membrane and through exocytosis release outside the cell to infect nearby cell. The immune response: the cellular RNA receptors like, RIG-I and MDA-5 recognized the dsRNAs in cytoplasm, activating the pro-inflammatory response and antiviral response inside cells. The cytokines activate the macrophages and lymphocytes to kick start both cellular and humoral response. c The virus disseminates to the other part of body through blood affecting the brain, heart, liver spleen, large intestine, kidneys