The second wave of COVID-19, which is caused by the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading
over the world. The mechanism behind the escaping from current
antivirals is still not clear, due to the occurrence of continuous
variants in SARS-CoV-2 genomes. Brazil is the world’s second most
COVID-19-affected country. In the present study, we identified the
genomic and proteomic variants of Brazilian SARS-CoV-2 isolates. We
identified 16 different genotypic variants were found among the 27
isolates. The genotypes of three isolates such as Bra/1236/2021 (G15),
Bra/MASP2C844R2/2020 (G11), and Bra/RJ-DCVN5/2020 (G9) have a unique
mutant in NSP4 (S184N), 2’O-Mutase (R216N), membrane protein (A2V) and
Envelope protein (V5A). A mutation in RdRp of SARS-CoV-2, particularly
the change of Pro to Leu at 323 resulted in the stabilization of the
structure in BRA/CD1739-P4/2020. NSP4, NSP5 protein mutants are more
virulent in Genotype 15 and 16. A fast protein folding rate changes the
structural stability and leads to escape for current antivirals. Thus,
our findings help researchers to develop the best potent antivirals
based on the new mutant of Brazilian isolates.