The pandemic caused by SARS-CoV-2 which has emerged from China has devastated whole humanity. The genome of SARS-CoV-2 and several viruses belonging to Coronaviridae family (severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV)) have been sequenced and annotated. The genome sequence similarity of SARS-CoV-2 confirms it is a beta coronavirus [1, 2]. It appears that spike glycoprotein expressed on the surface of SARS-CoV-2 is responsible facilitating the entry of the virus into the host cells, this is the resultant of strong binding with angiotensin-converting enzyme 2 (ACE 2) of the host cells [3, 4]. This SARS-CoV-2 infection disturbs the host immune system with elevated Th17 response ; this is where people with low immunity are prone for fatal consequences.
Characterization of spike glycoprotein is important in understanding its mode of entry and in the development of therapeutics against SARS-CoV-2. All coronaviruses enter into host cells utilizing spike glycoprotein which gives coronaviruses a crown-like appearance by forming spikes on their surface. The analysis of spike glycoprotein amino acid sequence shows a large ectodomain, a single-pass transmembrane anchor, and a short C-terminal intracellular tail . The ectodomain includes a receptor-binding unit S1 and a membrane-fusion unit S2. The results of electron microscope showed spike glycoprotein consists of a clove-shaped spike with three S1 heads and a trimeric S2 stalk. The entry of virus to host cell is facilitated by S1 which binds to the ACE 2 through receptor-binding domain (RBD), while S2 fuses host cell membrane with viral envelope allowing the viral genome to enter into host cell. Specific RBD-receptor binding determines if a cell can be infected and also serves as a target for therapeutic developments to treat diseases caused by coronaviruses [7, 8].
This SARS-CoV-2 infection to the host cells, coronaviruses utilizes a multi-subunit RNA-synthesis complex of viral non-structural proteins (NSP) responsible for the replication and transcription of the viral genome. The SARS-CoVNSP12 polymerase is associated with two other essential proteins, NSP7 and NSP8. The N-terminal of NSP12 contains a common structure which is conserved in all coronaviral polymerases as a large structure having kinase-like fold bound by two NSP8 molecules. This demonstrates NSP12 complex a potent therapeutic target in the development anti-coronaviral drugs .
The 7.27 million confirmed cases of SARS-CoV-2 and mortality over 413,000 as of 12 June, 2020, has made all the countries to search for effective therapeutic modalities in the treatment of COVID-19. One of the approved lists of drugs in the treatment of COVID-19 is remdesivir; it inhibits NSP 12 and thereby prevents RNA synthesis and kills the virus. This remdesivir molecular formula is C27H35N6O8P; the structure appears to have prominent naphthalene ring . The remdesivir treatment has side effects on the liver and kidney functions and this is an FDA-approved drug in the treatment of COVID-19; earlier, it was used in the treatment of Ebola infection [10, 11].
In India and other parts of Asia, large number of medicinal plant extracts and their derivatives are largely used in the treatment of various ailments including viral diseases. Andrographolide a major constituent present in the leaf extract of Andrographis paniculata (AP) is used as herbal medicine which possesses antiviral, antibacterial, anti-inflammatory effects, and stabilizes Th1/Th2/Th17 responses [12,13,14]. The chemical name of andrographolide is 3α, 14, 15, 18-tetrahydroxy-5β, 9βH, 10α-labda-8, 12-dien-16-oic acid γ-lactone, and its molecular formula is C20H30O5. The structure of andrographolide has been analyzed by using X-ray, 1H,13 C-NMR, and ESI-MS . Even though andrographolide is not very soluble in water, it is soluble in acetone, chloroform, ether, and hot ethanol. Crystalline andrographolide reported to be highly stable up to 3 months . The structure of remdesivir and andrographolide has one common naphthalene ring, and andrographolide is smaller than remdesivir [9, 15]. These evidences encouraged us to comprehend the anti-SARS-CoV-2 effect of andrographolide. In this study, we used in silico approach to dock andrographolide structure to RBD and NSP12 protein structures of SARS-CoV-2 to predict that AP extract can be used for anti-coronaviral treatment.