Table 2.

Molecular activity of non-structural proteins.

Non-structural proteins
Non-structural protein	Molecular functions	References
NS1	•The primary function is the replication of viral ssRNA. •Attaches to the dendritic cells (DCs) during viral infection and initiates the formation of pro-inflammatory chemokines and cytokines. •Instantly trigger immune cells that express toll-like receptor-4 (TLR4) and disrupt the cellular integrity of endothelial cells by activating the secretion of proinflammatory chemokines and cytokines.	[[53], [54], [55], [56]]
NS2A	•Key role in virion assembly by recruiting viral ssRNA, structural proteins, and proteolytic enzymes to the area of virion assembly. •Coordinates nucleocapsid and virus formation. •Antagonization of immune response of the host.	[[57], [58], [59]]
NS2B	•Its prime role is to confirm the regulation of the proteolytic activity of the virus. •Modify the permeability property of membrane or membrane destabilization. Act as a co-factor of NS3 for serine protease activity.	[[60], [61], [62], [63]]
NS3	•Cleaves the polyprotein in association with NS2B via serine protease enzyme activity. •Upwind duplex RNA to initiate viral ssRNA genome synthesis by ATPase/helicase activity. •It shows specific NTPase activity for regulating the NS5 protein. •The activity of RNA triphosphatase is crucial for the replication of viral RNA and the capping process. •It diminishes glycolytic activity by interacting with glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[[64], [65], [66], [67], [68]]
NS4A	•Modulates the ATPase activity of the helicase protein of NS3. •Subverts innate immune response of the host by targeting mitochondrial antiviral signaling protein (MAVS).	[[69], [70], [71]]
NS4B	•Collaboratively helps in the replication of viral ssRNA and the anti-host responses. •It can interfere with the phosphorylation of signal transducer and activator of transcription (STAT)-1 to block the Interferon alpha/beta (IFN-α/β) influenced signal transduction cascade.	[[72], [73], [74], [75]]
NS5	•Enzymatic activity and significant function in the replication of viral ssRNA. •Down-regulation of immune interferon response into the host cell via interacting with STAT-2. •Regulating RNA splicing activity in the host cell.	[[76], [77], [78]]