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.