VV116 as a potential treatment for COVID-19

Expert Opinion on Pharmacotherapy, Journal Year: 2023, Volume and Issue: 24(6), P. 675 - 678

Published: March 18, 2023

Introduction VV116 is a chemically-modified version of the antiviral remdesivir with oral bioavailability and potent activity against SARS-CoV-2.Areas Covered The optimal treatment standard-risk outpatients who develop mild-to-moderate COVID-19 controversial. While several therapeutic are currently recommended, including nirmatrelvir–ritonavir (Paxlovid), molnupiravir, remdesivir, these treatments have substantial drawbacks, drug-drug interactions questionable efficacy in vaccinated adults. Novel options urgently needed.Expert Opinion On 28 December 2022, phase 3, observer-blinded, randomized trial was published evaluating 771 symptomatic adults high risk progression to severe disease. Participants were assigned receive 5-day course either Paxlovid)\, which recommended by World Health Organization for treating COVID-19, or primary end point time sustained clinical recovery through day 28. Among study subjects, found be noninferior Paxlovid respect fewer safety concerns. This manuscript examines what known about explores how this novel option may used future address ongoing SARS-CoV-2 pandemic.

Language: Английский

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Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization including BQ.1.1, CA.3.1, CH.1.1, XBB.1.16, and XBB.1.5

Antibody Therapeutics, Journal Year: 2023, Volume and Issue: 6(2), P. 108 - 118

Published: April 1, 2023

Abstract SARS-CoV-2 Omicron variant XBB.1.5 has shown extraordinary immune escape even for fully vaccinated individuals. There are currently no approved antibodies that neutralize this variant, and continued emergence of new variants puts immunocompromised elderly patients at high risk. Rapid cost-effective development neutralizing is urgently needed. Starting with a single parent clone neutralized the Wuhan-Hu-1 strain, antibody engineering was performed in iterative stages real time as emerged using proprietary technology called STage-Enhanced Maturation. An panel broadly neutralizes circulating obtained by vitro affinity maturation phage display. The engineered show potent neutralization BQ.1.1, XBB.1.16, surrogate virus test pM KD all variants. Our work not only details novel therapeutic candidates but also validates unique general strategy to create current future

Language: Английский

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New star-shaped ligands generated by evolutionary fitting the Omicron spike inner-cavity

Published: April 25, 2023

Predictions generated by evolutionary docking of star-shaped ligands targeting the prefusion state Omicron variants are described here. For this, one selected molecule previously identified with seeSAR program, was used as parent to randomly generate made-on-demand large children libraries for best fitting spike top-to-bottom inner-cavity DataWarrior subprogram. The docking-scores were consensed AutoDockVina ranks normalized molecular size and hydrophobicity. These explorations new main chemotype improved specificity exceptional nanomolar affinities, predicting aqueous soluble molecules trimeric alpha-helices.

Language: Английский

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Distinctive Features of the XBB.1.5 and XBB.1.16 Spike Protein Receptor-Binding Domains and Their Roles in Conformational Changes and Angiotensin-Converting Enzyme 2 Binding

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12586 - 12586

Published: Aug. 9, 2023

The emergence and the high transmissibility of XBB.1.5 XBB.1.16 subvariants SARS-CoV-2 omicron has reignited concerns over potential impact on vaccine efficacy for these future variants. We investigated roles mutations structure spike protein’s receptor-binding domain (RBD) its interactions with host cell receptor ACE2. To bind to ACE2, RBD must transition from closed-form open-form configuration. found that XBB variants have less stable structures may make easier. enhance RBD–ACE2 in compared XBB.1.5. observed significant structural changes loop motif regions RBD, altering well-known antibody-binding sites potentially rendering primary RBD-specific antibodies ineffective. Our findings elucidate how subtle contribute subvariants’ fitness their predecessors.

Language: Английский

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Predicting antibody and ACE2 affinity for SARS-CoV-2 BA.2.86 and JN.1 with in silico protein modeling and docking

Frontiers in Virology, Journal Year: 2024, Volume and Issue: 4

Published: July 19, 2024

The emergence of SARS-CoV-2 lineages derived from Omicron, including BA.2.86 (nicknamed “Pirola”) and its relative, JN.1, has raised concerns about their potential impact on public personal health due to numerous novel mutations. Despite this, predicting implications based solely mutation counts proves challenging. Empirical evidence JN.1’s increased immune evasion capacity in relation previous variants is mixed. To improve predictions beyond what possible counts, we conducted extensive silico analyses the binding affinity between RBD different (Wuhan-Hu-1, BA.1/B.1.1.529, BA.2, XBB.1.5, BA.2.86, JN.1) neutralizing antibodies vaccinated or infected individuals, as well human angiotensin-converting enzyme 2 (ACE2) receptor. We observed no statistically significant difference JN.1 other variants. Therefore, conclude that new have pronounced escape infection compared However, minor reductions for both ACE2 were noted JN.1. Future research this area will benefit structural memory B-cell should emphasize importance choosing appropriate samples studies assess protection provided by vaccination infection. Moreover, fitness benefits genomic variation outside need be investigated. This contributes understanding variants’ health.

Language: Английский

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