Question

What is the biochemical mechanism of COVID-19? How does it interact with its host cells? Explain why it causes respiratory distress.

Answer 1

Corona viruses are the part of the coronaviridae family. The get their name from the crown like spikes in their outer surface.

The glycoprotein spikes on the outer surfaces of the virus aid them to attach and enter the host cell. This glycoproteins are corded by specific genes in the ORF1 downstream region. This spike proteins have a 3D structure in the RBD region that helps in maintaining the van der Waals forces. The human ACE2 receptors lysine 31 residue recognises the glutamine 394 residue present in the RBD region. After binding to the ACE 2 receptor there are certain conformational changes in the spike protein and the viral envelope fuses through the cell membrane via the endosomal pathway. Here the virus releases its RNA and the host ribosomes translate the sequences in the ORF1a region to form viral poly proteins pp1a and 1ab. These are then cleaved in to small products by viral proteinase. Then a series of subgenomic RNAs are produced translated in to viral proteins and then assembled in the endoplasmic reticulum and golgi apparatus. Then this viral particles are released via exocytosis.

When the virus enters the cell various receptors like TLR4 might recognise the spike proteins and then subsequently activate the NF-kappa-B factors and the MAPK pathways which inturn produces proimflammatory proteins. Other pathways like the JAK-STAT pathway are also activated which causes the release of cytokines like IFN-alpha, IFN-gamma, IL-1beta, IL-6,IL-12 etc which causes hyper inflammation and eventually lead to acute respiratory distress syndrome.