Chemical Curiosity

What is COVID-19?

SARS-CoV-2, a new betacoronavirus of zoonotic origin, has produced the worst pandemic (coronavirus disease 2019, COVID-19) since the Spanish Flu. Apart from the lung, the virus can attack the cardiovascular system (Liu et al., 2020), kidneys, the digestive tract, and the central nervous system. Approximately 20% of the cases lead to severe complications (Chen et al., 2020), with varying estimates of the case fatality rate (CFR) (Baud et al., 2020; Kim and Goel, 2020). The reproductive number (R_o) in Wuhan, China was reported to be between 2 and 3 (Li et al., 2020).

How are the Lungs and the Airways Affected?

SARS-CoV-2, after gaining access to the respiratory system, binds to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2) to enter the host cells, using the serine protease TMPRSS2 for S protein priming (Hoffmann et al., 2020). ACE2 and TMPRSS2 were previously implicated in the disease progression of SARS epidemic, also caused by a closely related coronavirus (Li et al., 2003; Matsuyama et al., 2010). Coronaviruses, including SARS-CoV-2, use the class I fusion “spike” protein (S protein) to attach themselves to cell surface receptors, before being taken up into endosomes and releasing the viral genome into the cytoplasm (Fehr and Perlman, 2015). Structural features of the crucial S protein for SARS-CoV-2 have been established (Lan et al., 2020; Wang et al., 2020; Wrapp et al., 2020), and it’s a viable target for vaccines in development (Amanat and Krammer, 2020).

In the lungs, ACE2 is abundantly expressed on the surfaces of type 2 alveolar epithelial cells (Qi et al., 2020). Destruction of these cells may reduce the production of lung surfactants, which may in turn, negatively impact the gas-exchange function of the alveoli. Recent single cell RNA sequencing by researchers at the Wellcome Sanger Institute indicates that other epithelial cells in the airway, especially nasal epithelial cells also express ACE2 receptors (Sungnak et al., 2020).

Did Anyone See This Coming?

It’s well known that Chinese bats (especially horseshoe bats) are a potent reservoir of coronaviruses (Menachery et al., 2015). Although east Asia been through a pandemic caused by coronavirus before (SARS), COVID-19 has surprised most countries outside east Asia through its high transmissibility coupled with a large percentage of infected (and infectious) population that’s asymptomatic.

What are the Implications for India?

There are a few advantages for the Indian population: (a) a very hot summer (droplet transmission may be less effective at high temperatures), (b) a relatively young population, and (c) the promptness of the central and state governments in imposing a fairly strict lock-down. However, there are a few factors that work against disease containment: (a) the quality of the public healthcare system, (b) a large migrant population, and (c) the difficulty of contact-tracing and isolation in a country of 1.4 billion people. I expect (this is a guess) that we would reach a peak in hospitalizations in May, with a drop-off in the next four months. I’m not sure whether to expect a re-emergence in October–November.

References:

1. Amanat, F., and Krammer, F. (2020). SARS-CoV-2 Vaccines: Status Report. Immunity 52, 583-589.

2. Baud, D., Qi, X., Nielsen-Saines, K., Musso, D., Pomar, L., and Favre, G. (2020). Real estimates of mortality following COVID-19 infection. Lancet Infect Dis.

3. Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., et al. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395, 507-513.

4. Fehr, A.R., and Perlman, S. (2015). Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 1282, 1-23.

5. Hoffmann, M., Kleine-Weber, H., Schroeder, S., Kruger, N., Herrler, T., Erichsen, S., Schiergens, T.S., Herrler, G., Wu, N.H., Nitsche, A., et al. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 181, 271-280 e278.

6. Kim, D.D., and Goel, A. (2020). Estimating case fatality rates of COVID-19. Lancet Infect Dis.

Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., et al. (2020). Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, doi: 10.1038/s41586-41020-42180-41585.

7. Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., Ren, R., Leung, K.S.M., Lau, E.H.Y., Wong, J.Y., et al. (2020). Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 382, 1199-1207.

8. Li, W., Moore, M.J., Vasilieva, N., Sui, J., Wong, S.K., Berne, M.A., Somasundaran, M., Sullivan, J.L., Luzuriaga, K., Greenough, T.C., et al. (2003). Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450-454.

9. Liu, P.P., Blet, A., Smyth, D., and Li, H. (2020). The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation, doi: 10.1161/CIRCULATIONAHA.1120.047549.

10. Matsuyama, S., Nagata, N., Shirato, K., Kawase, M., Takeda, M., and Taguchi, F. (2010). Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J Virol 84, 12658-12664.

11. Menachery, V.D., Yount, B.L., Jr., Debbink, K., Agnihothram, S., Gralinski, L.E., Plante, J.A., Graham, R.L., Scobey, T., Ge, X.Y., Donaldson, E.F., et al. (2015). A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med 21, 1508-1513.

12. Qi, F., Qian, S., Zhang, S., and Zhang, Z. (2020). Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun, doi: 10.1016/j.bbrc.2020.1003.1044.

13. Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., Talavera-López, C., Maatz, H., Reichart, D., Sampaziotis, F., et al. (2020). SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine, doi: 10.1038/s41591-41020-40868-41596.

14. Wang, Q., Zhang, Y., Wu, L., Niu, S., Song, C., Zhang, Z., Lu, G., Qiao, C., Hu, Y., Yuen, K.Y., et al. (2020). Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell.

15. Wrapp, D., Wang, N., Corbett, K.S., Goldsmith, J.A., Hsieh, C.L., Abiona, O., Graham, B.S., and McLellan, J.S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260-1263.