Intro: Viruses, including SARS-CoV-2, which causes COVID-19, are constantly changing. These genetic changes (aka mutations) occur over time and can lead to the emergence of new variants that may have different characteristics. After the first SARS-CoV-2 genome was published in early 2020, scientists all over the world soon realized the immediate need to obtain as much genetic information from as many strains as possible. However, understanding the functional significance of the mutations harbored by a variant is important to assess its impact on transmissibility, disease severity, immune escape, and the effectiveness of vaccines and therapeutics.
Methods: Here in Canada, we have developed an interactive framework for visualizing and reporting mutations in SARS-CoV-2 variants. This framework is composed of three stand-alone yet connected components; an interactive visualization (COVID-MVP), a manually curated functional annotation database (pokay), and a genomic analysis workflow (nf-ncov-voc). Findings: COVID-MVP provides (i) an interactive heatmap to visualize and compare mutations in SARS-CoV-2 lineages classified across different VOCs, VOIs, and VUMs; (ii) mutation profiles including the type, impact, and contextual information; (iii) annotation of biological impacts for mutations where functional data is available in the literature; (iv) summarized information for each variant and/or lineage in the form of a surveillance report; and (v) the ability to upload raw genomic sequence(s) for rapid processing and annotating for real-time classification.
Discussion: This comprehensive comparison allows microbiologists and public health practitioners to better predict how the mutations in emerging variants will impact factors such as infection severity, vaccine resistance, hospitalization rates, etc.
Conclusion: This framework is cloud-compatible & standalone, which makes it easier to integrate into other genomic surveillance tools as well. COVID-MVP is integrated into the Canadian VirusSeq data portal (https://virusseqdataportal.ca) - a national data hub for SARS-COV-2 genomic data. COVID-MVP is also used by the CanCOGeN and CoVaRR networks in national COVID-19 genomic surveillance.
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http://dx.doi.org/10.1016/j.ijid.2023.04.006 | DOI Listing |
Bioelectrochemistry
January 2025
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo 09210-580, Brazil. Electronic address:
Owing to fast SARS-CoV-2 mutations, biosensors employing antibodies as biorecognition elements have presented problems with sensitivity and accuracy. To face these challenges, antibodies can be replaced with the human angiotensin converting enzyme 2 (ACE-2), where it has been shown that the affinity between ACE-2 and the receptor binding domain (RBD) increases with the emergence of new variants. Herein, we report on Ni-doped ZnO nanorod electrochemical biosensors employing an ACE-2 peptide (IEEQAKTFLDKFNHEAEDLFYQS-NH) as a biorecognition element for detecting Spike (S) Wild-Type (WT) protein.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139.
Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose "foundational" PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), which fine-tunes foundational models for antibody-sequence inputs by supervising on antibody structure and binding specificity examples.
View Article and Find Full Text PDFJ Virol
January 2025
Infection Biology Unit, German Primate Centre - Leibniz Institute for Primate Research, Göttingen, Germany.
The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).
View Article and Find Full Text PDFMol Biotechnol
January 2025
Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.
The etiological agent for the coronavirus disease 2019 (COVID-19), the SARS-CoV-2, caused a global pandemic. Although mRNA, viral-vectored, DNA, and recombinant protein vaccine candidates were effective against the SARS-CoV-2 Wuhan strain, the emergence of SARS-CoV-2 variants of concern (VOCs) reduced the protective efficacies of these vaccines. This necessitates the need for effective and accelerated vaccine development against mutated VOCs.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Chemical Sciences, University of Naples "Federico II", Via Cintia, 21, 80126 Napoli, Italy; CEINGE Advanced Biotechnologies s.c.a r.l. "Franco Salvatore", Via Gaetano Salvatore 486, 80131 Napoli, Italy. Electronic address:
SARS-CoV-2 encodes a 3C-like protease (3CL) that is essential for viral replication. This cysteine protease cleaves viral polyproteins to release functional nonstructural proteins, making it a prime target for antiviral drug development. We investigated the inhibitory effects of halicin, a known c-Jun N-terminal kinase inhibitor, on 3CL.
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