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Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 11097

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Special Issue Editors

Dr. Jordi Pérez-Tur

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Guest Editor

Instituto de Biomedicina de Valencia-CSIC, Unidad de Genética Molecular, 46010 Valencia, Spain
Interests: LRRK2 gene; Parkinson; PARK8-linked Parkinson's disease
Special Issues, Collections and Topics in MDPI journals

Dr. Fernando Cardona

E-Mail Website
Guest Editor

Instituto de Biomedicina de Valencia-CSIC, 46010 Valencia, Spain
Interests: genetics; molecular biology; biochemistry; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

More than a year into the SARS-CoV-2 pandemic, the amount of knowledge gathered so far is impressive. This issue aims to summarize what is known about it, from the virus to the host to therapies, including the mechanisms underlying the infection, host response, effects on pathology, and the evolution of the virus and of the pandemic, and which therapeutic strategies should be followed.

It is now clear that SARS-CoV-2 variants contribute to the extent of infection and spread of the virus and may play a role in the immune response, either acquired or induced by vaccination. In addition, host genetics and gene expression regulation have been shown to be key in the response to the infection. Interferon genetics and regulation, levels of the human receptor ACE2 or the protease TMPRSS22, and blood group are examples of how the host’s genetic condition affects the response. The molecular interaction between the S protein and its receptor is another important question in this disease. Besides ACE2, another membrane receptor with high genetic variability, Neuropilin-1, is involved in some aspects of the infection, e.g., the spread of the virus in the olfactory bulb and the central nervous system. For both receptors, it is still unclear how genetic or viral variants affect their interaction and thus the entry of the virus into the cell. Finally, all this knowledge should be translated into the design of therapeutic strategies, through both pharmacologic or epidemiologic interventions.

In this issue, we invite review and original articles that focus on any aspect of SARS-CoV-2 biology, COVID-19 processes, and, in general, any manuscript dealing with related subjects.

Dr. Jordi Pérez-Tur
Dr. Fernando Cardona
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

COVID-19
SARS-CoV-2
host genetics
viral genetics
gene expression
molecular interaction
structural biology
genetic variation
genetic epidemiology
GWAS
genome sequencing
epigenetics
blood groups
genetic susceptibility
risk factors
molecular intervention
long-COVID drug design
SARS-CoV-2, SARS-CoV, MERS-CoV
coronavirus biology
coronavirus variants

Published Papers (6 papers)

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Editorial

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4 pages, 201 KiB

Open AccessEditorial

Special Issue “Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease”

by Fernando Cardona and Jordi Pérez-Tur

Int. J. Mol. Sci. 2024, 25(9), 4670; https://doi.org/10.3390/ijms25094670 - 25 Apr 2024

Viewed by 470

Abstract

We are pleased to present the first and second editions of this Special Issue, titled “Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease”, of the International Journal of Molecular Sciences [...] Full article

(This article belongs to the Special Issue Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease 2.0)

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Research

Jump to: Editorial

14 pages, 2562 KiB

Open AccessArticle

Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes

by Laia Llucià-Carol, Elena Muiño, Natalia Cullell, Jara Cárcel-Márquez, Miquel Lledós, Cristina Gallego-Fabrega, Jesús Martin-Campos, Joan Martí-Fàbregas, Ana Aguilera-Simón, Anna M. Planas, Marta L. DeDiego, Alicia de Felipe Mimbrera, Jaime Masjuan, Sebastián García-Madrona, Tomás Segura, Esther González-Villar, Gemma Serrano-Heras, Ana Domínguez Mayoral, Paloma Menéndez-Valladares, Joan Montaner, Isabelle Migeotte, Souad Rahmouni, Gilles Darcis, David Bernardo, Silvia Rojo, Eva C. Schulte, Ulrike Protzer, Lisa Fricke, Christof Winter, Mari E. K. Niemi, Mattia Cordioli, Pilar Delgado and Israel Fernández-Cadenas Show full author list Hide full author list

Int. J. Mol. Sci. 2023, 24(17), 13452; https://doi.org/10.3390/ijms241713452 - 30 Aug 2023

Cited by 1 | Viewed by 1757

Abstract

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10⁻², se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = −0.04, p-value = 1.3 × 10⁻³, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10⁻⁴, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10⁻², se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection. Full article

(This article belongs to the Special Issue Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease 2.0)

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20 pages, 6352 KiB

Open AccessArticle

Integrating AI/ML Models for Patient Stratification Leveraging Omics Dataset and Clinical Biomarkers from COVID-19 Patients: A Promising Approach to Personalized Medicine

by Babatunde Bello, Yogesh N. Bundey, Roshan Bhave, Maksim Khotimchenko, Szczepan W. Baran, Kaushik Chakravarty and Jyotika Varshney

Int. J. Mol. Sci. 2023, 24(7), 6250; https://doi.org/10.3390/ijms24076250 - 26 Mar 2023

Cited by 4 | Viewed by 2604

Abstract

The COVID-19 pandemic has presented an unprecedented challenge to the healthcare system. Identifying the genomics and clinical biomarkers for effective patient stratification and management is critical to controlling the spread of the disease. Omics datasets provide a wealth of information that can aid in understanding the underlying molecular mechanisms of COVID-19 and identifying potential biomarkers for patient stratification. Artificial intelligence (AI) and machine learning (ML) algorithms have been increasingly used to analyze large-scale omics and clinical datasets for patient stratification. In this manuscript, we demonstrate the recent advances and predictive accuracies in AI- and ML-based patient stratification modeling linking omics and clinical biomarker datasets, focusing on COVID-19 patients. Our ML model not only demonstrates that clinical features are enough of an indicator of COVID-19 severity and survival, but also infers what clinical features are more impactful, which makes our approach a useful guide for clinicians for prioritization best-fit therapeutics for a given cohort of patients. Moreover, with weighted gene network analysis, we are able to provide insights into gene networks that have a significant association with COVID-19 severity and clinical features. Finally, we have demonstrated the importance of clinical biomarkers in identifying high-risk patients and predicting disease progression. Full article

(This article belongs to the Special Issue Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease 2.0)

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16 pages, 2194 KiB

Open AccessArticle

Revealing the Molecular Interactions between Human ACE2 and the Receptor Binding Domain of the SARS-CoV-2 Wild-Type, Alpha and Delta Variants

by Cécilia Hognon, Emmanuelle Bignon, Antonio Monari, Marco Marazzi and Cristina Garcia-Iriepa

Int. J. Mol. Sci. 2023, 24(3), 2517; https://doi.org/10.3390/ijms24032517 - 28 Jan 2023

Cited by 2 | Viewed by 2109

Abstract

After a sudden and first spread of the pandemic caused by the novel SARS-CoV-2 (Severe Acute Respiratory Syndrome—Coronavirus 2) wild-type strain, mutants have emerged which have been associated with increased infectivity, inducing surges in the contagions. The first of the so-called variants of concerns, was firstly isolated in the United Kingdom and later renamed Alpha variant. Afterwards, in the middle of 2021, a new variant appeared called Delta. The latter is characterized by the presence of point mutations in the Spike protein of SARS-CoV-2, especially in the Receptor Binding Domain (RBD). When in its active conformation, the RBD can interact with the human receptor Angiotensin-Converting Enzyme 2 (ACE2) to allow the entry of the virions into cells. In this contribution, by using extended all-atom molecular dynamic simulations, complemented with machine learning post-processing, we analyze the changes in the molecular interaction network induced by these different strains in comparison with the wild-type. On one hand, although relevant variations are evidenced, only limited changes in the global stability indicators and in the flexibility profiles have been observed. On the other hand, key differences were obtained by tracking hydrophilic and hydrophobic molecular interactions, concerning both positioning at the ACE2/RBD interface and formation/disruption dynamic behavior. Full article

(This article belongs to the Special Issue Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease 2.0)

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11 pages, 4078 KiB

Open AccessArticle

Detection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia

by Javier Perez-Florido, Carlos S. Casimiro-Soriguer, Francisco Ortuño, Jose L. Fernandez-Rueda, Andrea Aguado, María Lara, Cristina Riazzo, Manuel A. Rodriguez-Iglesias, Pedro Camacho-Martinez, Laura Merino-Diaz, Inmaculada Pupo-Ledo, Adolfo de Salazar, Laura Viñuela, Ana Fuentes, Natalia Chueca, The Andalusian COVID-19 Sequencing Initiative, Federico García, Joaquín Dopazo and Jose A. Lepe

Int. J. Mol. Sci. 2023, 24(3), 2419; https://doi.org/10.3390/ijms24032419 - 26 Jan 2023

Cited by 3 | Viewed by 1887

Abstract

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity. Full article

(This article belongs to the Special Issue Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease 2.0)

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15 pages, 1468 KiB

Open AccessArticle

The Association of PLAUR Genotype and Soluble suPAR Serum Level with COVID-19-Related Lung Damage Severity

by Ludmila A. Nekrasova, Anna A. Shmakova, Larisa M. Samokhodskaya, Karina I. Kirillova, Simona S. Stoyanova, Elena A. Mershina, Galina B. Nazarova, Kseniya A. Rubina, Ekaterina V. Semina and Armais A. Kamalov

Int. J. Mol. Sci. 2022, 23(24), 16210; https://doi.org/10.3390/ijms232416210 - 19 Dec 2022

Cited by 3 | Viewed by 1588

Abstract

Uncovering the risk factors for acute respiratory disease coronavirus 2019 (COVID-19) severity may help to provide a valuable tool for early patient stratification and proper treatment implementation, improving the patient outcome and lowering the burden on the healthcare system. Here we report the results of a single-center retrospective cohort study on 151 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected symptomatic hospitalized adult patients. We assessed the association of several blood test measurements, soluble urokinase receptor (uPAR) serum level and specific single nucleotide polymorphisms of ACE (I/D), NOS3 (rs2070744, rs1799983), SERPINE1 (rs1799768), PLAU (rs2227564) and PLAUR (rs344781, rs2302524) genes, with the disease severity classified by the percentage of lung involvement on computerized tomography scans. Our findings reveal that the T/C genotype of PLAUR rs2302524 was independently associated with a less severe lung damage (odds ratio 0.258 [0.071–0.811]). Along with high C-reactive protein, fibrinogen and soluble uPAR serum levels turned out to be independently associated with more severe lung damage in COVID-19 patients. The identified factors may be further employed as predictors of a possibly severe COVID-19 clinical course. Full article

(This article belongs to the Special Issue Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease 2.0)

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