**2. Disease biology**

SARS-CoV-2 is a novel corona virus. It is spherical and enveloped. SARS-CoV-2 spans 50–200 nM in diameter. It also contains a typical crown like appearance of coronaviruses due to the presence of 20 nM long spikes like structure on its surface (**Figure 1**). Corona viruses are divided into four genera: alpha-coronavirus (α-CoV), betacoronavirus (β-CoV), gamma-coronavirus (γ-CoV), and delta-coronavirus (δ-CoV). SARS-CoV-2 belongs to β-CoV genera. SARS-CoV-2 is a positive-sense, single-stranded RNA virus with large 29 Kb genome size [16, 17]. Genome wide study demonstrates that SARS-CoV-2 has sequence similarity with the human and bat corona viruses with 82% and 89% sequence homology, respectively [18]. Protein

**Figure 1.** *Schematic diagram showing SARS-CoV-2 structure.*

mapping reveals the common protein interaction networks among three CoVs (SARS-CoV-1, MERS-CoV, and SARS-CoV-2) in humans, hence identified molecular mechanisms and potential therapeutic interventions [19]. Genome organization includes sequences for leader region, UTRs, replicase, Spike, Envelope, Membrane, Nucleocapsid protein, 3′UTR, and poly (A) tail sequence [20]. The spike (S), membrane (M), envelope (E), and nucleocapsid (N) are the main four structural proteins of SARS-CoV-2 (**Figure 2**). Spike protein is a club-shaped protein present on the surface of virus and also capable of inducing neutralizing antibodies. It plays a major role in pathogenesis of SARS-CoV-2. M protein is the conserved and abundant protein, which helps virus to maintain its shape. It is also important during budding of viral particles from host cells. Role of E protein is important in viral pathogenesis. Like M protein, E is also a conserved one. Spike, E, and M together form the envelope of SARS-CoV-2. Viral RNA and N protein construct the nucleocapsid of virus [21, 22]. SARS-CoV-2 infects the upper respiratory tract in humans and cause common cold and flu-like infections. Patients suffer from influenza, sore throat, fever, cough, fatigue, and shortness of breath; in few cases, patients also experience gastrointestinal issues, such as diarrhea and vomiting. Severity leads to multiorgan failure and thus causes death [23, 24]. Old age people and individuals suffering from diabetes, hypertension, pulmonary disease, asthma, bronchitis, and cardiovascular disorders are at high risk of severe case of corona disease [24]. It has been reported that bats are the natural reservoir of SARS-CoV-2 like for other human CoVs. SARS-CoV-2 was initially transmitted to humans from infected

**Figure 2.** *Genome organization of SARS-CoV-2.*

animals in the Wuhan market and then spread globally when human-to-human contact occurs via respiratory droplets or aerosols of infected [16].

At molecular level, when the receptor binding domain of spike protein interacts with human-ACE2 (angiotensin-converting enzyme 2) receptor, it facilitates the binding and subsequent entry of viral particles into host cells. The spike is a heavily glycosylated protein and made up of two subunits, the S1 and the S2. The S1 subunit is again divided into two domains, that is, an N-terminal (S1 NTP) and a C-terminal domain (S1 CTP). RBD is present in C terminal S1 CTP. The RBD shows genomic variability. RBD determines the cellular tropism and host range to be infected by virus [25–27]. Different strains of Corona viruses have variation in binding affinity or human ACE2, thus differ in infection ability, transmission rate, and pathogenicity. In comparison to SARS-CoV (~31 nM) and MERS-CoV (~16.7 nM), SARS-CoV-2 binding affinity (~4.7 nM) is very high [28].
