Abstract
The World Health Organization reports that SARS-CoV-2 has infected over 220 million people and claimed over 4.7 million lives globally. While there are new effective vaccines, the differences in behavior of variants are causing challenges in vaccine development or treatment. Here, we discuss Delta, a variant of concern, and Lambda, a variant of interest. They demonstrate high infectivity and are less responsive to the immune response in vaccinated individuals. In this review, we briefly summarize the reason for infectivity and the severity of the novel variants. Delta and Lambda variants exhibit more changes in NSPs proteins and the S protein, compared to the original Wuhan strain. Lambda also has numerous amino acid substitutions in NSPs and S proteins, plus a deletion in the NTD of S protein, leading to partial escape from neutralizing antibodies (NAbs) in vaccinated individuals. We discuss the role of furin protease and the ACE2 receptor in virus infection, hotspot mutations in the S protein, the toxicity of the S protein and the increased pathogenicity of Delta and Lambda variants. We discuss future therapeutic strategies, including those based on high stability of epitopes, conservation of the N protein and the novel intracellular antibody receptor, tripartite-motif protein 21 (TRIM21) recognized by antibodies against the N protein.
Highlights
SARS-CoV-2, the cause of COVID-19, is a pathogenic member of the Coronavirinea subfamily and Betacoronavirus genera, which consists of an enveloped, unsegmented, single-stranded, positive sense RNA of ~29.9 kb [1,2]
The bottom half depicts the non-structural proteins encoded by ORF1a (NSP1-11) and ORF1b (NSP12-16), 11 order [3,21]
In SARS-CoV-2, a significant 12-nucleotide insertion results in an insertion of a 4 amino acid sequence (PRRA), including dibasic residues at positions 682 to 685, the junction of the S1/S2 domain. This position is cleaved by furin, which may facilitate a viral tropism in the host body and make SARS-CoV-2 more pathogenic than previous coronaviruses [38]
Summary
SARS-CoV-2, the cause of COVID-19, is a pathogenic member of the Coronavirinea subfamily and Betacoronavirus genera, which consists of an enveloped, unsegmented, single-stranded, positive sense RNA of ~29.9 kb [1,2]. Various studies have been conducted to identify the structure of the proteins of the virus to determine the reason for the higher infectiousness of the Delta and Lambda variants in comparison with the previous lineages. Microorganisms 2021, 9, 2167 virus, spike protein (S) plays a crucial role in pathogenicity by attaching to the host cell. This property of the spike protein has prompted attention for its use in vaccine development. This paper reviews the reason for the high infectivity and vaccine evasion of Delta and Lambda, focusing on the role of the S protein in increasing the infectivity, considering other proteins of the virus as potentially better therapeutic targets
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