Discussion
SARS-CoV-2 or commonly known as COVID-19 is a novel RNA coronavirus that
has caused significant morbidity and mortality around the globe and
continues to spread rapidly (Coronavirus disease 2019 (
COVID-19): situation report, 64 , 2020). As of the
24th of March 2020, according to the WHO situation
report 64, the current confirmed cases are 372,757 and 16,231 deaths
since the first reports in early January 2020 (Coronavirus disease
2019 ( COVID-19): situation report, 64 , 2020). Therefore, there is an
urgent need for new therapeutic regimes such as a vaccine against this
novel aggressive contagion. To this end, a promising SARS-CoV-2 antigen
candidate for vaccine development is the characteristic surface (spike)
glycoprotein of the virus. Several current clinical trials are looking
at developing vaccines for SARS-CoV-2. However, the success of these
trials depends on the vaccine providing protective immunity against the
virus. Recently, it has been shown that SARS-CoV-2 enters the epithelial
cells via interaction of its surface glycoprotein with the human
angiotensin-converting enzyme 2 (ACE2) found on the surface of the
epithelium (Hoffmann et al., 2020; Yan et al., 2020). This study sought
to investigate the emergence of mutations in the surface glycoprotein of
SARS-CoV-2 and their implications on the development of an effective
vaccine to disrupt the entry of the virus into human cells.
Sequences for the surface glycoprotein of SARS-CoV-2 from different
isolates in the GISAID and GenBank databases were analyzed for mutations
using Multiple clustalW Sequence alignment. In this study, the first
sequenced SARS-CoV-2 genome from China was used as a reference to map
the mutations to (Tang et al., 2020). The analysis found that SARS-CoV-2
is rapidly evolving and is acquiring mutations that may cause antigenic
drift as seen in influenza viruses (Boni, 2008). It was found that the
surface glycoprotein had 64 different mutations in the protein sequence
from the pool of 796 SARS-CoV-2 isolates analyzed from around the world.
This rapid mutation rate combined with the highly infectious nature of
the virus has great implications for the development of a therapeutic
vaccine. The 1918 pandemic caused by the H1N1 influenza virus, infected
over one-third of the global population and killed over 40 million
people (Taubenberger, 2005). Current vaccines for influenza need to be
updated seasonally to catch up on the rapid mutation rates of the virus,
particularly in the haemagglutinin (HA) protein which is used by the
virus to enter epithelial cells (Boni, 2008).
SARS-CoV-2 enters the host cell through binding to the surface-bound
ACE2 enzyme (Tai et al., 2020). The mode of entry is through the
interaction of the receptor-binding domain (RBD) of the surface
glycoprotein with the ACE2 host cell membrane enzyme (Yan et al., 2020).
Therefore, disrupting this interaction through the production of
neutralizing antibodies has important implications for vaccine
development. However, continuous mutations in this region need to be
considered for the optimal design of vaccine antigens. The analysis from
this study found that among the 796 isolates, 12 substitution mutations
were identified in the RBD of the surface glycoprotein in 19 isolates
originating from China, USA and Europe. Therefore, it is critical that
mutations in the RBD region of the surface glycoprotein need to be
considered in the design of any vaccine.
Antigenic drift is the process by which viruses accumulate multiple
mutations in the sequence of proteins that the immune system recognizes
as non-self and mount neutralizing antibodies against (Carrat &
Flahault, 2007). If enough mutations accumulate over time in the viral
proteins, the immune system can longer recognize the viral antigens and
as such this can cause a significant epidemic or pandemic (Both, Sleigh,
Cox, & Kendal, 1983). SARS-CoV-2 is a novel virus to which there are no
current vaccines in clinical use, while several accelerated clinical
trials are underway to develop a vaccine. This study reports that
SARS-CoV-2 is rapidly moving towards antigenic drift as shown by the
sequence of one isolate from Belgium (Belgium_BA-02291_2020) which
contains substitutions K458R, H519P, D614G, T941A, and S943P.
Furthermore, K458R and H519P are located in the RBD region of the
surface glycoprotein, which suggests the virus may be evolving to
improve its binding capacity the ACE2 host surface enzyme. Also, of
significance is the fact that Belgium_BA-02291_2020 has most likely
evolved from one of the other 51 isolates in Belgium which had the D614G
and S943P substitutions. Another isolate from China
(Beijing_IVDC-BJ-005_2020) was found to contain substitutions V860C,
L861K, and F970S, indicating possible antigenic drift.
To conclude, this study has established that the SARS-CoV-2 surface
glycoprotein is rapidly mutating and evolving. More importantly, the
virus is moving rapidly towards antigenic drift and this has important
implications for the development and efficacy of a vaccine.
The sequence analysis of the
surface glycoprotein from SARS-CoV-2 has shed light on the rapid nature
of SARS-CoV-2 to mutate which needs to be considered in future studies
investigating possible therapeutics against the virus.