Table 1.

Critical proteins of SARS-CoV-2 and their mechanistic role (Poduri et al., 2020; Thakur et al., 2020).

Type of protein	Mechanistic role
SARS-COV-2 protein
S protein	Glycosylated transmembrane fusion protein (type I) is made of 1160–1400 amino acids. Involved in the attachment to the host cell via the ACE2 receptor. Cleaved by TMPRSS2 at the junction of hydrophobic fusion peptide into two subunits, S1 and S2.
S1 subunit	Also known as N-terminal or upper domain. It possesses a receptor-binding domain (RBD) responsible for ACE2 receptor binding. S1 domain is considered to be highly vulnerable to undergo mutation due to evolutionary pressure and its contact with the immune system of the host. This domain is further subdivided into SD-1 and SD-2 which induces conformational modifications in the C-terminal domain once bound to ACE2 receptors.
S2 subunit	Also called as C-terminal or lower domain. This domain is much more stable with the evolutionary process and thus less susceptible to undergo mutation. This domain consists of fusion machinery involved in the fusion of virus envelope with the host cell membrane
M protein	This is the most abundant protein in SARS-CoV-2 and responsible for eliciting a virus-specific humoral response and neutralizes developed antibodies against the virus inside the host cell
N protein	The protein is responsible for encapsulating and protecting (+)-RNA containing the genome of SARS-CoV-2. Also, assist in virion release by allowing a favourable orientation for virion at perinuclear membranes that further help in the release of virus particles.
E protein	This is a transmembrane protein acting as an ionophore. It assists in the release of viral genomic material inside a host cell in conjugation with human protease.
Non-structural proteins (Nsp 1–16)	The NSP complex is involved and associated with the central dogma of the viral genome. The complex assists and catalyzes viral RNA synthesis, proofreading, capping, and ultimately translation to allow synthesis of polyproteins (pp1a and pp1ab). Only necessary NSPs are discussed herewith
Nsp3	Also called papain-like protease (PLpro). This enzyme possesses the deubiquitinase property and suppresses the innate immune system of the host to allow damage to the virus. These enzymes are also involved in the cleavage of pp1a and pp1ab, thus catalyzing numerous functional and effector proteins.
Nsp7-Nsp8	This is also called a primase complex, involved in de novo initiation and primer extension during translation of viral mRNA
Nsp12	Important Nsp also called RNA dependent RNA polymerase; RdRp. It catalyzes the transcription and replication of RNA strand complementary to a given RNA template of the virus, allowing the synthesis of sgRNA along with structural, and accessory proteins
Nsp13	Also called zinc-binding helicase (HEL). This is involved in the initiation of replication, allowing the unwinding of duplex RNA/DNA with 5′ss tail in 5′–3′ direction
Nsp10/Nsp16 complex	This category of Nsp is a type of 2′O-methyltransferases enzymes. Nsp14 is involved with N7-(guanine)-methyltransferase, and Nsp16 is found to link with 2′O-methyltransferases activity, and both are involved with the modification of RNA cap structure.
Nsp14-16	This complex is involved with RNA proofreading.
Host proteins
ACE2	Widely distributed in the human body. Exist as soluble (cleaved) and insoluble (full length) form, both of which contain two domains, a protease domain and the catalytic domain. The protease domain is known to be involved with the S1 binding of SARS-CoV-2, and the catalytic domain is known to play a physiological role (formation of form Ang1-7). The binding of spike protein with protease domain of ACE2 allows its downregulation and thereby diminishes its protective role, which is further deteriorated at latter stages of Covid-19 that involves ACE2 internalization
TMPRSS2	It is a transmembrane serine protease (type II) enzyme known to cleaves the S protein at the hydrophobic monobasic site (685/686 junction) into two domains, S1 and S2.