Spike D614G variant became prevalent at the global level within a few months after observation of original strain, D614G Variant high affinity with human ACE2 receptor in comparison to the parental strain. The D614G mutation was able to increase replication capacity and susceptibility in both human and animal models and high disease severity was observed in a patient with the D614G variant (Korber et al., 2020; Plante et al., 2021). A high level of neutralizing antibodies was analyzed in animal models with the D614G variant, and compared with the parental strain (Chen LL et al., 2021; Ozono et al., 2021). Vaccine and therapeutics agents are less effective against D614G (Korber et al., 2020). TheD614G in the Furin binding is prominent common mutations described in nearly all the new variants (Ozono et al., 2021).

In Dec 2020, B.1.1.7 (Alpha) of SARS-CoV-2 was reported in the United Kingdom (Oude Munnink et al., 2021). Seventeen mutations were observed in the viral genome, of which eight mutations were in the spike (S) protein such as Δ69-70 deletion, Δ144 deletion, N501Y, A570D, P681H, T716I, S982A, D1118H. Another important mutation N501Y has shown an increased severity of the infection and high binding affinity of the spike protein to ACE 2 receptors, enhancing the viral attachment and subsequent entry into host cells (Cascella et al., 2021). This variant was observed in the UK for the first time in September 2020, and in December 2020 in the USA (Galloway et al., 2021). The mortality rate was observed to be high in B.1.1.7 variant infected patients and the adjusted hazard ratio was analyzed as 1.67, 95% CI 1.34-2.09 (Cascella et al., 2021). The B.1.1.7 dominant variant SARS-CoV-2 strain is circulating in various countries globally (Port et al., 2021). BNT162b2-immunized individuals with B.1.1.7 mutations was observed a substantial reduction in neutralization titters (Emary et al., 2021; Kernéis et al., 2021). Persons immunized with Ad26.COV2-S observed a neutralization effect against the B.1.1.7 variant in-vitro, but was less effective than against the reference strain (Emary et al., 2021). NVX-CoV2373 SARS-CoV-2 vaccine was investigated and observed more effective (86%) against B.1.1.7 variant in comparison to the original strain (96%). The phase III clinical trial was evaluated with 15,000 participants (18 and 84 years of age) in the UK (Galloway et al., 2021; Shinde et al., 2021). The efficacy of AZD1222 was observed 70% in patients with B.1.1.7. In the case of non-B.1.1.7 Lineages, 77% efficacy was observed (Lopez Bernal et al., 2021). Various amino acid modifications have been observed in the spike protein of B.1.1.7. including P681H, N501Y, 69/70, E484K, and ORF8 mutations (Collier et al., 2021; Kernéis et al., 2021; Seghatchian, 2021). Another mutation F888L in the spike protein was also identified in the Nigerian variant along with the E484K (Port et al., 2021; Ashoor et al., 2021). This mutation has been reported to alter the biological efficiency of SARS-CoV-2 by performing the hydrolysis by TMPRSS2 and augmenting viral invasion (Ashoor et al., 2021; Liu C et al., 2021). It is also probable that this major variation supports the viruses’ misleading of the immune response of the host (Kernéis et al., 2021; Liu J et al., 2021; Quinonez et al., 2021). All the above investigations were carried out with their limitations in respect to methodology, sample size, and immune response (Kernéis et al., 2021).

The B.1.351 variants were reported in South Africa in December 2020 (Shinde et al., 2021). B.1.351 variants carry E484K mutations and cause more severe symptoms than the other variants (Hoffmann et al., 2021). Emergent mutant variants from the UK and South Africa are more infectious, but effective against developed vaccines (Voysey et al., 2021). The 501.V2 variants was the first time observed in South Africa, it carries K417N and E484K mutations. The 501.V2 are more transmissible and cause severe in comparison to the parental strain (Wang et al., 2021). E484K mutation also plays an important role in immune mechanism, host receptor affinity, and infectivity (Shastri et al., 2021). Initial findings have indicated that the Oxford–AstraZeneca vaccine has shown considerable reduction in effectiveness against these variants and was reviewed by the WHO (Lopez Bernal et al., 2021). Novavax can protect up to a moderate level, while the Pfizer–BioNTech and Johnson & Johnson vaccines also have reduced the efficacy against the β-lineage, although for the other vaccines the data is not yet available (Heath et al., 2021; Sadoff et al., 2021; Lopez Bernal et al., 2021). It has also been identified that the most extensively distributed vaccines may have reduced antibody neutralization against Beta variants of SARS-CoV-2, which is relevant to how vaccines can stop the disease by reducing asymptomatic infection (Grint et al., 2021). Sera from patients immunized with the Moderna and Pfizer-BioNTech vaccines had less activity against Beta (B.1.351) (Bates et al., 2021). On 1 April 2021, an investigation on a Pfizer/BioNTech South African vaccination analysis showed that the vaccine has been 100% effective against Beta variants (Seppälä et al., 2021). In January 2021 Ad26.COV2. S Vaccine developed by Johnson & Johnson has been tested in South Africa and reported 72% efficiency against SARS-CoV-2 infection (mild to severe) in the US and 57% in South Africa (Shinde et al., 2021; Voysey et al., 2021).

The Cluster 5 Variant may decrease the strength of immune defenses, after a decrease in the viral neutralization sensitivity which is obtained by vaccination and the normal procedure of infection (Becker et al., 2021). In Denmark, ΔFVI-spike was categorized as Cluster 5 strains transmitted from mink worsened the situation and may further aggravate it. As of November 2020, active mink-mediated corona cases are confirmed (Lassaunière et al., 2021). As per WHO data, the cluster 5 variant resisted diminishing sensitivity to countering antibodies. Viral expansion in mink lakes leads to a recurring risk of human infection from mink, and the adaptability of this variant in mink is a huge health concern in the future (Hoffmann et al., 2021).

This variant was identified in the Czech Republic and Slovakia in late 2020, within the clade B.1.258 (Brejová et al., 2021). It has been observed to escape the immune response and increase the severity of infection. This variant has been analyzed with an N439K mutation in the terminal regions of the spike glycoprotein while showing similar deletions 69-70 at the receptor-binding domain (RBD) (Gómez et al., 2021). H69/V70 deletions mutations have been modified. The antigenic peptides in the amino-terminal region are changed, subsequent in confrontation to neutralization by improving sera and vaccination (Jeong et al., 2021).

A new variant has been observed in Lineage P.1 with 11 mutations in the spike protein. Since December 2020, approximately 42% of SARS-CoV-2 positive tested samples were analyzed with P.1 lineage infection (Hoffmann et al., 2021). These mutations are closely linked with antibody-mediated immune evasion high infection rate (+161%), the mortality rate was also observed to be high, up to 50%, making it 2.2 times more transmissible than the baseline virus (Sarkar et al., 2021). P.1 and P.1-like clades are more infective in younger people. P.1 or 20 J/501Y.V3 were classified as gamma mutations (K417T, E484K, and N501Y) in the RBD domain (Hirotsu and Omata, 2021). P.1 or 20 J/501Y.V3 variants with E484K substitution were reported in Brazil (Hirotsu and Omata, 2021). In November 2020 and January 2021, it has been observed that the Gamma variant is 1.4-2.2 times more infectious than baseline (Hitchings et al., 2021). People who have been completely vaccinated with Pfizer or Moderna have shown significant neutralization against Gamma variants (Planas et al., 2021). The data from various clinical trials carried out by the WHO, CoronaVac, and BBIBP-CorV shows effectiveness against Gamma variants (Barros-Martins et al., 2021). They also found that Oxford–AstraZeneca, and CoronaVac had preserved antibody neutralization against Gamma linage, and Pfizer–BioNTech and Moderna had minimal to moderate reduction in neutralization, with no information for other vaccines so far (Barros-Martins et al., 2021).

Three major substitution mutations were observed in Lineage B.1.617 and B.1.617.2, namely P681R, L452R, and E484Q (Liu J et al., 2021). Two substitution mutations were observed in the RBD domain, and one nearby the furin binding the site, which increases the mode of transmission (+64%), hospitalization (+85), and mortality, with natural immunity also affected. The chances of reinfection were decreased, but the efficacy of the vaccine was also compromised in Lineage B.1.617 and B.1.617.2 (Lopez Bernal et al., 2021). Various investigations were examined by the WHO and found that vaccines from Oxford–AstraZeneca, and Pfizer–BioNTech, are likely to sustain efficacy/effectiveness against delta’s variants. (Liu J et al., 2021). Researchers from the field also investigated and found that the vaccines produced by Oxford–AstraZeneca have shown a reduced neutralization effect against the Delta virus (Pascarella et al., 2021). Spike protein mutations D111D, E484Q, G142D, and P681R are found in the delta variants of 15 mutations, which may escape antibody neutralization. Initial observations have shown that Emergent variants reduce the efficacy of the mRNA-based vaccine (Cherian et al., 2021). Researchers from the field also explored whether the E484K variant may compromise the efficiency of the current vaccine. More clinical investigation is required to finally reach a conclusion for therapeutic strategies against new variants.

Lineage B.1.168 was observed in West Bengal, India with two amino acid deletions, Tyr145 and His146, and E484K and D618G mutations (Cherian et al., 2021). These substitutions can escape convalescent plasma and multiple monoclonal antibodies (Bates et al., 2021). Other 1.5.9 variants are also reported in different countries (Singh et al., 2021). The B.1.429 or Epsilon lineage was reported in 50% of samples in Los Angeles, which exhibits different mutations in ORF1ab and spike protein (Shen et al., 2021). The variants B.1.429 and B.1.427 were classified as VOCs by the CDC (Shen et al., 2021). These variants with D1183Y and I4205V mutations in the ORF1ab and S13I, W152C, and L452R mutations in the spike protein are also known as CAL.20C, 20C/S:452R, CA VUI, or 21C. CAL.20C variants were identified in November 2020 in California, this variant was classified Epsilon (McCallum et al., 2021). The prevalence of the variant in sequenced samples from Northern California increased from 3% to 25% between November and December 2020 in total samples tested in California (Zhang et al., 2021). In January 2021, the prevalence of the variant 20G was observed in the United States. This variant was also seen in some SARS-CoV-2 cases in Europe, Asia, and Australia (McCallum et al., 2021). The frequency of this variant was decreased in February 2021, until April 2021 by when this Epsilon variant had disappeared from southern California and comprised just 3.2 percent of cases were observed in the United States, while 2/3 cases were observed from Alpha variants (Zhang et al., 2021). Theta variants (P.3.) were reported on February 18, 2021, with two mutations E484K and N501Y, by the Central Visayas Department of the health service of the Philippines (Oude Munnink et al., 2021). Theta variants (theta) were also identified in Japan, the United Kingdom, and Malaysia in July 2021. Theta variants disappeared by July 2021. Another, the R.1 variant was reported by Japan on the RBD of the spike protein with E484K mutation, and another W152L mutation was observed in the N-terminal Domain. These mutations also play an important role in immune evasions, and are reported by various countries at the global level (Chen RE et al., 2021). The Pfizer-BioNTech vaccine was shown to be 94% effective in preventing R.1 infected hospitalization and mortality. As Alpha and then Delta increase in Japan, R.1 illustrations are becoming increasingly rare (Kernéis et al., 2021). Linage B.1.620 was analyzed in Lithuania in March 2021, also known as the Lithuanian strain, it was found in Central Africa, North America, France, and Belgium. In an analysis of the original variant, this lineage revealed 23 substitutions, most of which are discrete mutations (Silva et al., 2021; Korber et al., 2020). Lineage B.1.618 was discovered for the first time in October of 2020, this variant contained E484K mutation with many other variations and showed substantial development in West Bengal, India, in April 2021 (Biswas et al., 2021). On 23 April 2021, The PANGOLIN analysis identified 135 sequences in India (Singh et al., 2021). Sixteen cases in the United Kingdom were identified under Lineage B.1.1.318 as a VUI (VUI-21FEB-04) (Seghatchian, 2021).