**2. Genomics of SARS-CoV-2**

SARS-CoV-2, such as other coronaviruses, is an enveloped, single-stranded, and positive-sense RNA virus with a non-segmented genome of 30 kb (**Figure 1**) [12]. The viral genome encodes 16 nonstructural proteins (NSPs) needed for pathogenesis and virus replication, four structural proteins including envelope (E), membrane (M), nucleocapsid (N), and spike (S) glycoproteins, all of which are important for virus genotyping and therapeutic strategies, and nine other accessory genes (**Figure 1**) [13]. There is a huge similarity between the first published SARS-CoV-2 genome and SARS-CoV, especially in the spike protein revealing the high transmission rate from human to human [14].

There is a huge data rising on the viral genomics and its transcriptomic level involving the virus-host protein interactions. These data are highly needed for the drug discovery, vaccine development, and public health strategies.

The ACE2 gene expresses the angiotensin-converting enzyme-2 in several human cells. Several studies reported that the spike protein has a 10–20 times higher affinity for binding to the ACE2 receptor than SARS-CoV, which explains the SARS-CoV-2's higher transmission rate [15].

The host ACE2 receptor is located in abundance on epithelial cells that line the alveoli and bronchioles of the lungs, as well as endothelial cells and myocytes that line the pulmonary blood vessels [16]. The ACE2 gene is also expressed in the small intestine, which could clarify the gastrointestinal symptoms appeared with the viral infection [17].

The spike (S) protein is thought to be the key protein involved in viral entry into target cells [18].

The host transmembrane serine protease 2 (TMPRSS2) "primes" the S protein by cleaving it into two active domains: S1 and S2. The S1 domain can then engage with the ACE2 receptor, while the S2 subunit helps the virus fuse with the target cell, facilitating the viral entry [18]. Blocking the viral entry pathway through ACE2 and TMPRSS2 represents one of the therapeutic strategies that can prevent the virus attachment with the host cell.

#### **Figure 1.**

*(a) Illustrative representation of the SARS-CoV-2 genome presenting the location of the structural, nonstructural, and accessory proteins. The figure is created by BioRender program.*
