**1. Introduction**

The SARS-CoV-2 virus has been with us for more than 2 years now. More than half a billion people have contracted the virus in a little over 2 years, and more than 6 million people have died from the virus [1, 2]. Subsequent pandemic waves of the disease can be prevented by social distancing during local outbreaks and vaccination. In spite of current pandemic, coronaviruses have always been present and are commonly the cause of colds. The first virus from the family mentioned above, isolated in 1962,

#### **Figure 1.**

*The cross-section of SARS-CoV-2 with characteristic spikes at the virus's surface (left) and the fusion of the virus with the cell membrane (right). The figure is the artwork of David Goodsell (PDB-101: Educational resources supporting molecular explorations through biology and medicine [3]).*

was classified as an enveloped, single-stranded (+ssRNA) RNA virus. The new virus family was named after its characteristic morphological appearance, the crown spikes (spike protein or Spro) on its surface (**Figure 1**) [4].

Until the outbreak of the SARS (Severe Acute Respiratory Syndrome; causative virus named SARS-CoV) pandemic in mainland China and Hong Kong in 2003, coronaviruses did not receive so much attention from the scientific community. Timely action at that time prevented the outbreak and evolution to the pandemic. However, in 2012, the respiratory syndrome coronavirus (MERS-CoV) led to an outbreak of the Middle East respiratory syndrome (MERS) in Saudi Arabia, mainland China, the United Arab Emirates, and the Republic of Korea [2, 5, 6]. In late 2019, SARS-CoV-2, a member of the *Coronaviridae* family, emerged in Wuhan, China. As a result, a creeping spread among the human population began, and the WHO declared a pandemic on March 11, 2020 [7, 8]. At the time of writing, COVID-19 disease (caused by SARS-CoV-2) has spread worldwide, claiming more than 6.5 million lives. As the SARS-CoV-2 virus has become a critical health concern, scientists immediately began research on this topic. COVID-19 disease is of great concern worldwide because, while the majority of cases have mild symptoms, a variable percentage (0.2 to >5%!) of patients progresses to pneumonia and multiple organ failure, which can lead to death especially without medical assistance [9, 10].

Vaccines against SARS-CoV-2 are now available, few therapeutic options have been authorized for emergency use by FDA and only one antiviral agent has been approved for COVID-19 treatment, however novel drug research is ongoing [11–16]. Since vaccines are the poster child in the fight against the COVID-19 pandemic, a high viral mutation rate may lead to changes in the structures of essential viral proteins, rendering available vaccines ineffective [17]. This concern is exacerbated by the fact that, with the exception of inactivated SARS-CoV-2 vaccines, all other vaccines (RNA vaccines, Adenovirus-based and protein-based vaccines) currently in clinical use are targeted at the same structure in the virus – the spike protein from the viral envelope. Its biological functions and surface location, make it a major target for the formation of neutralizing antibodies. However, this also determines the high frequency of mutations in this region, which can help the virus escape from the immune response [18].

#### *Perspective Chapter: Bioinformatics Study of the Evolution of SARS-CoV-2 Spike Protein DOI: http://dx.doi.org/10.5772/intechopen.105915*

The first identified mutations and respectively recognized subtypes / variants of the virus were announced in March and April 2020 [19, 20]. In late 2020, the first SARS-CoV-2 variant of concern (VOC) was reported—the B.1.1.7 variant (UK variant, designated *alpha* by WHO as of June 7, 2021; https://www.who.int/). Alpha is often designated by canonical mutations: N501Y, 69/70 deletion, P681H. This was followed by the appearance of several other variants of concern—*beta, gamma, delta and omicron*, as well as a number of variants of interest (VOI; for variant classification the reader is referred to a wonderful classification at CDC: https://www.cdc.gov/ coronavirus/2019-ncov/variants/variant-classifications.html). The second in the list of VOC was B.1.351 variant (*beta;* canonical mutations: K417N, E484K, N501Y) or South African variant [21, 22]. Both variants carry an N501Y mutation in the RBD (receptor binding domain) of the Spro, which is associated with increased viral transmission [23]. In addition, the South African variant carries mutations K417N and E484K, which may be responsible for decreased binding to host antibodies [24]. P.1 (*gamma*, canonical mutations: K417T, E484K, and N501Y) variant has been reported in Brazil with the known N501Y, E484K and the novel K417T mutations [25]. *Epsilon* or B.1.427 or B.1.429 followed with canonical mutations: S13I, W152C, L452R, D614G. In early 2021, a novel SARS-CoV-2 variant B.1.617.2 (*delta*, canonical mutations: L452R, T478K, D614G, and P681R) nicknamed "the double mutant" or Indian variant was reported to cause infections in India and slowly spread throughout the world via global travel practices [26]. Acquired critical mutations in the Spro, particularly in the receptor-binding domain (RBD), are currently under heavy investigation (Delta Plus variant) as they may have higher infectivity and transmissibility or even escape the host immune response [27]. Last but not least is the observed *omicron* or B.1.1.529 variant first detected in Botswana and then in South Africa in November 2021. Omicron is described with at least 34 mutations in Spro, of which 15 are in RBD, 7 in the NTD and 3 close to the furin cleavage site.
