Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

Morton, Scott P.; Phillips, Joshua

doi:10.1109/bibm52615.2021.9669765

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…Later, the binding and the key contribution from the electrostatic interactions were confirmed by other research groups too using additional theoretical approaches (Bai & Warshel, 2020; K. Khan et al, 2021; Morton & Phillips, 2020; D. Wang et al, 2021; Y.…”

Section: Resultsmentioning

confidence: 64%

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

Giron

Laaksonen

Silva

2022

Preprint

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SARS-CoV-2 has caused immeasurable damage worldwide and available treatments with high efficacy are still scarce. With the continuous emergence of new variants of the virus, such as Omicron, Alpha, Beta, Gamma, and Delta - the so-called variants of concern, the available therapeutic and prevention strategies had to return to the experimental trial to verify their effectiveness against them. This work aims to expand the knowledge about the SARS-CoV-2 receptor-binding domain (RBD) interactions with cell receptors and monoclonal antibodies (mAbs). Special attention is given to the Omicron variant and its comparison with the others, including its sublineage BA.2 and two new ones (B.1.640.1 and B.1.640.2/IHU) recently found in France. By using constant-pH Monte Carlo simulations, the free energy of interactions between the SARS-CoV-2 receptor-binding domain (RBD) from different variants and several partners (Angiotensin-Converting Enzyme-2 (ACE2) polymorphisms and several mAbs) were calculated. It was evaluated both the impact of mutations for the RBD-ACE2 and how strongly each of mAb can bind to the virus RBD, which can indicate their therapeutic potential for neutralization. RBD-ACE2-binding affinities were higher for two ACE2 polymorphisms typically found in Europeans (rs142984500 and rs4646116), indicating that these types of polymorphisms may be related to genetic susceptibility to COVID-19. The antibody landscape was computationally investigated with the largest set of mAbs so far in the literature. From the 33 studied binders, groups of mAbs were identified with weak (e.g. S110 and Ab3b4), medium (e.g. CR3022), and strong binding affinities (e.g. P01prime, S2K146 and S230). All the mAbs with strong binding capacity could also bind to the RBD from SARS-CoV-1, SARS-CoV-2 wt, and all studied variants. These mAbs and especially their combination are amenable to experimentation and clinical trials because of their high binding affinities and neutralization potential for current known virus mutations and a universal coronavirus.

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Section: Resultsmentioning

confidence: 64%

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

Giron

Laaksonen

Silva

2022

Preprint

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“…Several factors have been demonstrated to affect the impact of VOCs. For example, it has been observed an increased effect at pH associated with nasal secretions (from 5.5 to 6.5) 28 . For this reason, additional experiments both in vitro and in vivo are needed to establish the biological significance of SARS‐CoV‐2 mutations and how the interactions between mutations and local cellular microenvironment influence the clinical outcome and the transmission dynamics of this virus.…”

Section: Discussionmentioning

confidence: 99%

SARS‐CoV‐2 B.1.617 Indian variants: Are electrostatic potential changes responsible for a higher transmission rate?

Pascarella

Ciccozzi

Zella

et al. 2021

Journal of Medical Virology

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Lineage B.1.617+, also known as G/452R.V3 and now denoted by WHO with the Greek letters δ and κ, is a recently described SARS‐CoV‐2 variant under investigation first identified in October 2020 in India. As of May 2021, three sublineages labeled as B.1.617.1 (κ), B.1.617.2 (δ), and B.1.617.3 have been already identified, and their potential impact on the current pandemic is being studied. This variant has 13 amino acid changes, three in its spike protein, which are currently of particular concern: E484Q, L452R, and P681R. Here, we report a major effect of the mutations characterizing this lineage, represented by a marked alteration of the surface electrostatic potential (EP) of the receptor‐binding domain (RBD) of the spike protein. Enhanced RBD‐EP is particularly noticeable in the B.1.617.2 (δ) sublineage, which shows multiple replacements of neutral or negatively charged amino acids with positively charged amino acids. We here hypothesize that this EP change can favor the interaction between the B.1.617+ RBD and the negatively charged ACE2, thus conferring a potential increase in the virus transmission.

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Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

Cited by 2 publications

References 24 publications

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies

SARS‐CoV‐2 B.1.617 Indian variants: Are electrostatic potential changes responsible for a higher transmission rate?

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