S-protein cleavage operates at two locations inside the S2 protein element, with the first cleavage dividing the receptor-binding domain from the fusion domain of the S-protein while second cleavage facilitate membrane fusion. 18, 19 Transmembrane protease serine 2 (TMPRRS2) or TMPRSS11D implement S1/S2 cleavage to invoke S-protein followed by viral and cellular membrane fusion. The virus must access the host cell cytosol following receptor binding by endosomal cysteine protease cathepsins. S1 and S2 are linked by a polybasic amino acid bridge, which might be important for viral targeting. The Protein Data Bank (PDB) model of this glycoprotein reveals how the subunits are formed of different regions that are fundamental to the infection process. (d) The S-protein of SARS-CoV2 comprises two subunits, S1 and S2, and is commonly represented as a sword-like spike.
(c) Schematic of the S-protein–receptor binding mechanism of SARS-CoV-2. (b) The genomic organization of SARS-CoV-2, highlighting the viroporins ORF3a (blue), E (green), and ORF8 (purple), as well as their propozed topology/3D structures. Genomic organization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Spike (S)-protein structure. 14, 15 Viral entry into the host cell is facilitated by endocytosis, for that virus uses human cell machinery. 12, 13 The S-protein attaches to the Angiotensin-converting enzyme 2 (ACE-2) receptor, which is found in the lung epithelia of the host.
Genetically, it contains nonsegmented positive-sense single-stranded RNA (ssRNA), which is encapsulated in a capsid formed of protein hence, it is an enveloped virus. The viral structure and genomic organization of SARS-CoV-2 are shown in Fig. 11 The S-protein has two domains or subunits in addition to the receptor-binding motif that is, an S1 subunit (bilobular receptor-binding domain) and an S2 subunit (stalk fusion domain). Its structural component mainly comprises five kinds of proteins: Spike protein (S), Membrane protein (M), Envelope protein (E), Nucleocapsid (N), and RNA Genome (R, 26-32 kb in length). 9 A coronavirus comprises a lipid bilayer wrapping with spike-like projections on a surface formed of glycoprotein. Since the first report of a coronavirus-related pneumonia outbreak in December 2019, the virus SARS-CoV-2 that triggers the COVID-19 has become a pandemic, with > 200 million people in over 220 countries reported to be infected and around three million people dying from COVID-19, as of May 2021. Nonreplicating viral vector (genetically modified virus)Īpproved in 93 countries, with WHO approval Jenner Institute (University of Oxford), Cobra Biologics, Oxford Biomedica, Merck KGaA, Halix BV, Pall Corporation, SGS, India’s Serum Institute, AstraZeneca, Catalent Biologics, CSL Limited Gamaleya Research Institute, Acellena Contract Drug Research, and DevelopmentĬOVID-19 Vaccine AstraZeneca (AZD1222) also known as Vaxzevria and Covishield LNP-encapsulated mRNA vaccine encoding S-proteinĪdv serotype 26(Ad26)vector-based DNA vaccine (nonreplicating viral vector)Īpproved in 41 countries with WHO approval 5 IgA can reach to upper respiratory tact through mucociliary process but only when the serum IgG concentration is high.Īpproved in 85 countries with WHO approval ) induces a strong serum IgG reflex that is believed to defend the lower respiratory tract but will not trigger the epithelial cell IgA responses (in both serum and respiratory fluids) necessary to protect the upper respiratory tract. 3, 4 Intramuscular administration ( Table 1 2 As of May 2, 2021, more than 189 candidate vaccines against SARS-CoV-2 were under different stages of early-stage (75 vaccine candidates under active investigation in animals) and clinical development (99 vaccines in clinical trials on humans). 1 More than 4.31 billion doses of COVID-19 vaccine have been administered across 180 countries at a rate of 42.5 million doses a day. Post vaccination, the adaptive immune response is mediated by B cells that produce antibodies and by T cells.
An ideal vaccine should provide rapid, multifaceted, long-term protection by preventing the disease from causing severe disease, hospitalization, and death. Vaccines take advantage of the remarkable capacity of the human immune system to respond to, and recall, pathogenic material it encounters.