Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge the immune system as it is found that neutralizing antibodies from prior infections or vaccines are less receptive to binding with the Delta spike protein. Here, we investigated the structural changes caused by the mutations in the Delta variant's receptor-binding interface and explored the effects on binding with the ACE2 receptor as well as with neutralizing antibodies. We find that the receptor-binding β-loop-β motif adopts an altered but stable conformation causing separation in some of the antibody binding epitopes. Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.
The emergence of antibiotic-resistance is a major concern to global human health and identification of novel antibiotics is critical to mitigate the threat.
We computationally investigated the role of the Omicron RBD mutations on its structure and interactions with surrounding domains in the spike trimer as well as with ACE2. Our results suggest...
The novel coronavirus (SARS-CoV-2) pandemic that started in late 2019 is responsible
for hundreds of millions of cases worldwide and millions of fatalities. Though vaccines
are available, the virus is mutating to form new strains among which are the variants
B.1.1.7 and B.1.351 that demonstrate increased transmissivity and infectivity. In this
study, we performed molecular dynamics simulations to explore the role of the mutations
in the interaction of the virus spike protein receptor binding domain (RBD) with the
host receptor ACE2. We find that the hydrogen bond networks are rearranged in the
variants and also that new hydrogen bonds are established between the RBD and ACE2 as a
result of mutations. We investigated three variants: the wild-type (WT), B.1.1.7, and
B.1.351. We find that the B.1.351 variant (also known as 501Y.V2) shows larger
flexibility in the RBD loop segment involving residue K484, yet the RBD–ACE2
complex shows higher stability. Mutations that allow a more flexible interface that can
result in a more stable complex may be a factor contributing to the increased
infectivity of the mutated variants.
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