New Habits - New Strains
Spacing and timing are essential to developing a habit. In the process, we may have to unlearn few habits. Doing similar things at the exact location and similar location will make you spend less energy and thinking, which is the crux of developing a new practice.
Once you develop a habit, the improvements you may see at the beginning may look small, but they may compound at a later point in time.
COVID forcefully made us develop a habit of wearing masks, following social distancing, and working from home. Due to the new practices, the number of asthma cases significantly reduced in many countries (south Korea, England, Israel). Doctors usually advise asthmatic patients to be careful about pests, secondhand smoke, and other significant concerns, including viruses, pollen, dust mites, and air pollution. The study opinioned that the reduced asthma attacks could be because of less exposure to viruses in recent times. The importance of the virus as a major irritant in asthma gained prominence. Doctors may now focus on virus exposure for asthma attacks as the masks are coming off and relaxing social distancing policies in many countries.
It is just not humans, the Coronavirus is also developing habits – which in turn showing increased spread in less time.
Sugarcoat on coronavirus: Glycans covering the spike and outer proteins dodge them from the immune system. These glycans protect the entire spike protein except the receptor-binding domain. Mutating the glycans supporting the RBD domain both in simulations and lab experiments collapsed the domain and reduced viral infections. Scientists are trying a way how to snipping glycans for therapeutic purposes.
Mutation on S1 protein: SARS-COV2 virus docs on ACE2 receptor of lung epithelial cells. The alpha variant has ten mutations in the receptor-binding domain, while the delta variant has many more variants that help the variants bind ACE2 with more affinity.
Using TMPRSS2 host protein: The new SARS-COV2 has developed another habit of entering the cells using TMPRSS2. TMPRSS2 cut the spike two proteins, allowing the hydrophobic region to expose and making the virus burry itself onto the host membrane. The entry of SARS-COV through cathepsin is not a healthy habit for the virus, as it involves being trapped in the endosome. Inhibitors of protease inhibitor (TMPRSS2) could a potential leads for SARS-COV2 in the next few years.
Competing host translation: After the virus injects RNA into the cell, it has developed a habit of competing with the host protein synthesis machinery. The viral proteins NSP1 delegate the host protein to systematically chop all the cellular mRNA that don’t belong to the virus (mRNA without viral tag).
Viral proteins (NSP1) control protein machinery (ribosomes) by blocking their entry gates– as a result, host mRNA can not access ribosomes for protein synthesis. Finally, the virus also turns off the alarm by blocking the exit channels of the nucleus so that none of the gene transcripts move out of the nucleus.
When host immune cells detect the viral infection, there is a massive load of the virus, and immune cells hyperactivate (cytokine storm) and cause severe damage to the host. Immunosuppressant like dexamethasone is effective by dampening the hyperactive immune response.
Once SARS-COV2 develops a habit of blocking the host’s protein synthesis, it works in expanding the launching pads. The virus-infected cells expressing ACE2 fuses together to form a massive industry (Syncytia) of viral particles. Inside the cell, the viral particles move into double-membrane vesicles of the endoplasmic reticulum (Golgi and lysosomes) to evade innate immune sensors.
The link between S1 and S2 subunits (5 aminoacids; proline, arginine, arginine, alanine, and arginine) has to be clipped by host protein furin to make virus spread. SARS-COV2 strains without furin action site did not transmit, while the coronavirus with intact furin site spread faster. Both alpha and delta adopted a new habit of mutating the amino acids into basic, which furin more effectively recognize and clips. More furin action makes the more spike proteins enter the cells.
Because of the new habits of sars-COV2, the virus can be detected after four days of infection vs. six days of infection for the original strain. The viral loads of the delta variant are more than 1000 times higher than the original strain. Shorten incubation time and more viral loads aiding in higher infection.