By Daniel Lo
The current outbreak Coronavirus Disease 2019 (COVID-19) was first emerged in December 2019 in Wuhan, China. COVID-19 is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has led to ~ 32 million cases of infection and over 977,000 deaths worldwide. It was then classified as a pandemic by the World Health Organisation (WHO) in March. This disease not only affect the economies and healthcare systems of countries, but also individuals and their family members are affected. This unprecedented pandemic requires a significant effort to deal with, yet the complete control of COVID-19 is still challenging and uncertain.
Coronaviruses (CoVs) are representation of a large family of viruses that cause respiratory tract infections ranging from mild illnesses (common cold) to more lethal varieties, such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS).
SARS-CoV-2 is a single-stranded RNA virus of roughly 30 kb genome size, which is one of the largest among RNA viruses. On entry to the host cell, the virus particle is uncoated, and the genome enters the cell cytoplasm. The coronavirus RNA genome acts like a messenger RNA and it is directly translated. Similar to other CoVs, the genomic organisation of SARS-CoV-2 of the 5’ side comprises of open reading frames ORF1a and ORF1b and occupying the first two-thirds of the genome. The ribosome translates ORF1a and ORF1b into two polyproteins, pp1a and pp1b. The genome of SARS-CoV-2 encodes for four structural proteins similar to other coronaviruses including: S (spike), E (envelope), M (membrane), and N (nucleocapsid) protein, which are required to make complete virus particle.
The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD). The RBD in the S protein is believed to mediate the binding of the virus to our host cells. When the S protein interacts with ACE2 receptor on the surface of our body cells, the virus will invade our bodies. If the ACE2 receptor hasn’t been found, the virus cannot invade our body’s cells. Hence, ACE2 receptors is believed to be a major target to block viral entry. The receptor binding motif (RBM) on the RBD forms the interface between the S protein and ACE2, and the RBM is composed with 2 regions. The stability of the RBD is maintained by the regions outside the RBM.
Infected carriers can transmit viruses into the environment; CoVs are transmitted from a host to another host. Human CoVs mainly target epithelial cells, infecting these cells of the respiratory tract. The interaction between the S protein of the coronavirus and the complementary cell receptors determines the infectivity, species range and the tissue trophism. For example, Severe acute respiratory syndrome–related coronavirus (SARS-CoV) infects the human epithelial cells of the lungs by binding to ACE2 receptor whereas DPP4 mediates the infection of coronaviruses in Middle East respiratory syndrome-related coronavirus (MERS-CoV). It was shown that DPP4 was not able to mediate the SARS-CoV-2 entry, so not all coronaviruses rely on ACE2 receptors to invade our bodies.
SARS-CoV-2 has a close genetical relationship as SARS-CoV which occurred in 2002 that caused the SARS outbreak in 2003. However, the latter has 774 deaths and a fatality rate of 9.7%. The SARS-CoV-2 is less deadly but more transmittable compared with SARS-CoV. The MERS outbreak has caused a high fatality rate of 34%, neither SARS nor MERS were classified as a global pandemic. To compare the ability of spreading of a pathogen, the basic reproduction number R₀ is used to estimate the number of secondary cases produced by a single infection. When R₀ is greater than 1, the epidemic is growing. The R₀ for SARS was estimated between 2.0 to 3.0 and reduced to 1.1; R₀ for MERS was 0.6 and R₀ for COVID-19 is approximately around 2.5. The motility rate of COVID-19 is 3.06% and the rate increases significantly with age. Similar patterns were observed with SARS.
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