Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19

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.

Clinical and Virological Features of patients hospitalized with different types of COVID-19 vaccination in Mexico City

“…Figure S3). Although this finding was not statistically significant in our study, other studies have reported more severe disease in infections associated with these lineages [10,42]. In particular, mutations in the spike (S) protein of the virus which confer a higher affinity of the S1 domain to the angiotensin converter enzyme 2 (ACE2) are one of the main reasons behind the higher pathogenicity of the Delta variant [42].…”

Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

“…Oral treatments of Covid-19, Molnupiravir and Paxlovid, have recently been issued an Emergency Use Authorization and are currently awaiting full approval by the FDA ( 4 , 5 ). Nevertheless, discovery of new anti-SARS-CoV-2 agents is urgently needed, especially for treating infections by highly transmittable variants ( 6 , 7 ).…”

High-throughput molecular dynamics-based alchemical free energy calculations for predicting the binding free energy change associated with the common mutations in the spike receptor-binding domain of SARS-CoV-2

“…The lambda (λ) variant is classified under C.37 lineage and was reported the first time in Peru in December 2020. This variant with L452Q and F490S mutations at RBD has also improved transmissibility and ability to evade vaccine elicited antibodies(27,28), while the following variant (B.1.1.7, alpha) is known for about a 50% higher transmission rate than the original SARS-CoV-2 virus(8). Due to the transmission advantage of the alpha variant and its sub lineage (B1.1.7 + E484K) over B.1 and B.1.1 lineages, it become the dominant variant in the UK in the end of 2020, spreading to the other parts of the world.…”