From the beginning of the pandemic, several variants of SARS-CoV-2 have been identified with the significant capability of transmission rate relative to the wild-type virus. These emerging variants, raising concerns about their impact on infectivity and mortality, as well as the effectiveness of current vaccines. The emerging variants have been reported from different countries across the world including South Africa (variant B.1.351) [[1]Tegally H. Wilkinson E. Giovanetti M. Iranzadeh A. Fonseca V. Giandhari J. et al.Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa.], Brazil (variant P.1) [[2]Resende P.C. Bezerra J.F. de Vasconcelos R.H.T. Arantes I. Appolinario L. Mendonça A.C. et al.Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil, January 2020.], United Kingdom (variant B.1.1.7) [[3]

Organization W.H. SARS-CoV-2 variant-United Kingdom of Great Britain and northern Ireland. Disease Outbreak News.

], and lately India (variant B.1.617) [[4]Expert reaction to cases of variant B.1.617 (the 'Indian variant') being investigated in the UK.], however, soon after of their detection, they have been reported in all other parts of the world. All these variants have mutations in different segments of their genomes relative to the wild type, however, the mutations in the spike receptor-binding domain (S-RBD) are a real challenge for the current vaccination program as many available vaccines are designed to produce neutralizing antibodies against S-RBD which react and block S-RBD interaction with human angiotensin-converting enzyme 2 (hACE-2) as virus receptor. Some variants have common mutations in their S-RBD. For example, N501Y mutation is shared between B.1.1.7, B.1.351, and P.1, or E484K mutation is sheared among B.1.351, and P.1. Some other variants have a different mutational signature in their S-RBD such as B.1.617 variant (E484Q, L452R, and P681R) [[4]Expert reaction to cases of variant B.1.617 (the 'Indian variant') being investigated in the UK.], highlighting the adaptive evolution of SARS-CoV-2 to a human host in a different geographical area. Recently, we performed an in-silica analysis and found that new variants (B.1.1.7, B.1.351, B.1.617 and P.1) of SARS-CoV-2 have different sensitivity to the neutralizing antibody (CV30). We found that the affinity of CV30 to spike protein decrease 90% for B.1.1.7 variant relative to wild type virus, while the affinity would decrease more; up to 30% for B.1.351, P.1 and B.1.617 variants relative to wild type [[5]Quinonez E. Vahed M. Hashemi Shahraki A. Mirsaeidi M Structural analysis of the novel variants of SARS-CoV-2 and forecasting in North America.]. In line with our findings, Wang et al, reported a small but significantly reduced activity of Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccines against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant [[6]Wang Z. Schmidt F. Weisblum Y. Muecksch F. Barnes C.O. Finkin S. et al.mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.]. Another study has also shown that the mutants carrying the N501Y mutation (such as B.1.1.7) are relatively resistant to a few mAbs targeting S-RBD and not more resistant to convalescent plasma or vaccinee sera, while B.1.351 variant is resistant to multiple mAbs targeting S-RBD and are markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccine sera (10.3-12.4 fold) [[7]Wang P. Nair M.S. Liu L. Iketani S. Luo Y. Guo Y. et al.Antibody resistance of SARS-CoV-2 variants B. 1.351 and B. 1.1. 7.]. No information is available about the neutralization activity of Ad26.COV2.S (Johnson & Johnson) and Sputnik V (Gamaleya) vaccines against the new variants. There is also no information available regarding the neutralization activity of AZD1222 (AstraZeneca) and BBIBP-CorV (Sinopharm) vaccines against B.1.1.7 and P.1, however, neutralization decreased by [8]Abdool Karim S.S. de Oliveira T New SARS-CoV-2 variants—clinical, public health, and vaccine implications.]. On the other hand, our forecast analysis (post-vaccination model), showing that the rate of B.1.1.7 will sharply decrease in North America in near future due to massive vaccination and higher sensitivity of this variant to neutralizing antibody (90%), but the frequency of B.1.351, B.1.617 and P.1 variants will gradually increase to 5% after herd immunity achieved [[5]Quinonez E. Vahed M. Hashemi Shahraki A. Mirsaeidi M Structural analysis of the novel variants of SARS-CoV-2 and forecasting in North America.]. May 16, 2021, CDC of the US announced that “fully vaccinated people can resume activities without wearing a mask or physically distancing, except where required by federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance” (https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html; retrieved on May 19, 2021). CDC considers people who pass 2 weeks after their second dose of the Pfizer or Moderna vaccines, or 2 weeks after a single dose of Johnson & Johnson's Janssen vaccine. Considering continues the adaptation of SARS-CoV-2 to transmission among humans, increasing the number of variants that can escape from neutralizing antibodies, different efficiency of current vaccines to neutralize the wild type and new variants and limited availability of vaccine supplies for many countries, we strongly believe to continue wearing a mask, practicing social distancing and following guidelines until at least 75% of population get vaccinated in many countries. The end of the pandemic is only possible when effective vaccines against circulating variants are distributed equitably across the world which would potentially eliminate virus transmission and more adaptation to humans. Some heavily populated countries such as India and Brazil are currently facing a strong wave of COVID-19 disease with high mortality caused by new variants (able to escape neutralizing antibodies; up to 30%). Limited availability of vaccine supplies for many countries will increase the odds of evolving new variants of SARS-CoV-2 to start a new pandemic with vaccine-resistant lineages. We strongly suggest formulating new vaccines covering all variants with low affinity (