Started in December 2019, we have been living in COVID-19 pandemic for over a year, as of today, there are 154 million confirmed cases and 3.19 million deaths globally. This pandemic is unprecedented, and it has caused severe damage not only to human health but global economy due to months of countrywide quarantine. The urge of controlling the spread of pandemics becomes stronger and stronger, thus, in order to overcome the current difficult situation, knowing the causative agent is the essential first step.
The causative agent for this pandemic is SARS-CoV-2, the seventh coronavirus that’s known to infect people, and the third Betacoronavirus that causes epidemics in humans, the previous ones are SARS-CoV and MERS-CoV. SARS-CoV-2 was first isolated from the patients who were admitted to local hospitals and have been to the Seafood and Wet Animal Market due to mystery pneumonia. Thus, epidemiologically, the market could be seen as the origin of SARS-CoV-2. By comparing the SARS-CoV-2 sequence with other known human coronaviruses’, not many similarities were found, hence it was considered as a novel coronavirus. Interestingly, though comparing alone the genome sequence of SARS-CoV-2 to the previous epidemic coronaviruses’, SARS-CoV-2 and SARS-CoV fell into two different clades, which means that SARS-CoV-2 did not evolve directly from SARS-CoV, by only comparing the spike protein sequence of SARS-CoV-2 to SARS-CoV spike, it showed extreme similarities between the two spike protein, a hypothesis of that SARS-CoV-2 might the same cell-entry mechanism as SARS-CoV was made and later proved to be correct.
The cell entry mechanism, in other words, how the virus gets into your cell, for both SARS-CoV-2 and SARS-CoV is binding viral spike protein to a cellular membrane receptor Angiotensin-Converting Enzyme(ACE2). This is interesting, because, in a healthy condition, ACE2 does not act as a receptor but a peptidase, which is an enzyme that cuts peptides, yet for SARS-CoV-2 infection, ACE2 plays the role of the receptor which initiates that cell entry mechanism. Many therapeutics for viral diseases have the targets the cell entry, SARS-CoV-2 is no exception. However, due to its rapid replication, experts are still looking for other more conserved targets for therapeutics. As mentioned before, the receptor binding step is an essential step for SARS-CoV-2 to initiate the cell entry mechanism, the other important step is cell fusion, which is a step that actually takes the virus into the cell, before the fusion starts, two cleavages have to be made in order to prime the spike protein to initiate cell fusion, the proteins that do the job of cleaving is TMPRSS2 and furin, TMPRSS2 is a protease, a protein that cuts protein and furin is a protein that only cut a specific region that contains conserved amino acids motif in order to activate the target. From previous studies, blocking either one of the cleavage enzymes would effectively reduce the pathogenesis, that says, reduce the replication ability of the virus.
Globally, there are 10 vaccines that have been developed and approved. Three are inactivated vaccines including CoronaVac, BBIBP-CorV that are from China and one from India (BBV152); two are mRNA vaccines, BNT162b2 from multination and mRNA-1273 from the US, worth mentioning, both of the vaccines are developed by pharmaceutical corporations (Pfizer and Moderna); three adenovirus vaccines AZD1222 from the UK, Sputnik V from Russia, and Ad5-nCoV from China; one non-replicating viral vector vaccine JNJ-78436735 from US and Netherland developed by (Johnson&Johnson); last but not the least, peptide-protein(EpiVacCorona) vaccine from Russia1.
However, the nature of rapid replication of RNA viruses, and the lack of proofreading leads to a higher mutation rate of SARS-CoV-2. As of now (May 2021), there are four major variants have known including B.1.1.7(UK variant), B.1.135 (South Africa variant), P.1 (Brazil variant), and B.1.617 (India variant). All of the variants have shown one or more mutations, mainly substitutions at where the spike protein of SARS-CoV-2 binds to ACE2 receptor, which multiple studies have shown that these variants have an increase of affinity to ACE2 receptor and increase of infectivity. So far, the most concerning mutations are the ones located in the receptor-binding domain because they would have a direct or indirect effect on binding to the receptor, ACE2. The main concern for the experts is whether the immunity protection built from previous infection or vaccine would still be able to protect the population from these variants, the short answer would be yes, but with an abolished efficiency. That says, the vaccine-induced antibodies’ activity probably would not be high enough to fight the variants after a period of time, thus one or many boosters might be needed in the future as a form like a flu shot.
Showing below is a timeline for SARS-CoV-2 and relative events:
- COVID-19 vaccine tracker. (n.d.). Retrieved May 2, 2021, from https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker