Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Research and Insights into COVID-19

Special Issue Editors
Special Issue Information
Keywords
Published Papers

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 (31 March 2024) | Viewed by 18596

Share This Special Issue

Special Issue Editors

Dr. Manuela Rizzi

E-Mail Website
Guest Editor

Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy
Interests: nanomaterials; biomaterials; regenerative medicine; toxicology; extracellular matrix
Special Issues, Collections and Topics in MDPI journals

Dr. Pier Paolo Sainaghi

E-Mail Website
Guest Editor

Internal Medicine Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
Interests: multiple sclerosis; autoimmune diseases; anti-rheumatic drug therapy; osteoporosis; hypovitaminosis D; chronic inflammatory demyelinating polyneuropathy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nowadays we are entering in the third year of COVID-19 pandemic, but molecular mechanisms underlying SARS-CoV-2 infection, host immune response and rationale of therapeutic interventions are not still fully understood. Even if the worldwide massive vaccination campaign reduced the risk of developing the most severe disease symptoms, the high tendency of SARS-CoV-2 to undergo genetic mutation accounts for the hard journey to the development of an effective therapy for COIVD-19.

This special issue aims to publish the most recent advances in molecular research on COVID-19, considering the pathogenic mechanisms as well as the host immune response and the molecular pathways activated by therapeutic interventions. Both original articles and comprehensive reviews dealing with molecular pathways involved in COVID-19 pathophysiology and disease resolution are welcomed for this special issue.

Dr. Manuela Rizzi
Dr. Pier Paolo Sainaghi
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

SARS-CoV-2
COVID-19
prognostic and diagnostic biomarkers
molecular mechanism of infection
molecular pathophysiology
immune response

Published Papers (13 papers)

Download All Papers

Research

Jump to: Review

19 pages, 3772 KiB

Open AccessArticle

Plasma Proteins Associated with COVID-19 Severity in Puerto Rico

by Lester J. Rosario-Rodríguez, Yadira M. Cantres-Rosario, Kelvin Carrasquillo-Carrión, Alexandra Rosa-Díaz, Ana E. Rodríguez-De Jesús, Verónica Rivera-Nieves, Eduardo L. Tosado-Rodríguez, Loyda B. Méndez, Abiel Roche-Lima, Jorge Bertrán and Loyda M. Meléndez

Int. J. Mol. Sci. 2024, 25(10), 5426; https://doi.org/10.3390/ijms25105426 - 16 May 2024

Viewed by 391

Abstract

Viral strains, age, and host factors are associated with variable immune responses against SARS-CoV-2 and disease severity. Puerto Ricans have a genetic mixture of races: European, African, and Native American. We hypothesized that unique host proteins/pathways are associated with COVID-19 disease severity in Puerto Rico. Following IRB approval, a total of 95 unvaccinated men and women aged 21–71 years old were recruited in Puerto Rico from 2020–2021. Plasma samples were collected from COVID-19-positive subjects (n = 39) and COVID-19-negative individuals (n = 56) during acute disease. COVID-19-positive individuals were stratified based on symptomatology as follows: mild (n = 18), moderate (n = 13), and severe (n = 8). Quantitative proteomics was performed in plasma samples using tandem mass tag (TMT) labeling. Labeled peptides were subjected to LC/MS/MS and analyzed by Proteome Discoverer (version 2.5), Limma software (version 3.41.15), and Ingenuity Pathways Analysis (IPA, version 22.0.2). Cytokines were quantified using a human cytokine array. Proteomics analyses of severely affected COVID-19-positive individuals revealed 58 differentially expressed proteins. Cadherin-13, which participates in synaptogenesis, was downregulated in severe patients and validated by ELISA. Cytokine immunoassay showed that TNF-α levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Ricans. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

11 pages, 1028 KiB

Open AccessArticle

The Immune Response of OAS1, IRF9, and IFI6 Genes in the Pathogenesis of COVID-19

by Malena Gajate-Arenas, Ingrid Fricke-Galindo, Omar García-Pérez, Angélica Domínguez-de-Barros, Gloria Pérez-Rubio, Roberto Dorta-Guerra, Ivette Buendía-Roldán, Leslie Chávez-Galán, Jacob Lorenzo-Morales, Ramcés Falfán-Valencia and Elizabeth Córdoba-Lanús

Int. J. Mol. Sci. 2024, 25(9), 4632; https://doi.org/10.3390/ijms25094632 - 24 Apr 2024

Viewed by 664

Abstract

COVID-19 is characterized by a wide range of clinical manifestations, where aging, underlying diseases, and genetic background are related to worse outcomes. In the present study, the differential expression of seven genes related to immunity, IRF9, CCL5, IFI6, TGFB1, IL1B, OAS1, and TFRC, was analyzed in individuals with COVID-19 diagnoses of different disease severities. Two-step RT-qPCR was performed to determine the relative gene expression in whole-blood samples from 160 individuals. The expression of OAS1 (p < 0.05) and IFI6 (p < 0.05) was higher in moderate hospitalized cases than in severe ones. Increased gene expression of OAS1 (OR = 0.64, CI = 0.52–0.79; p = 0.001), IRF9 (OR = 0.581, CI = 0.43–0.79; p = 0.001), and IFI6 (OR = 0.544, CI = 0.39–0.69; p < 0.001) was associated with a lower risk of requiring IMV. Moreover, TGFB1 (OR = 0.646, CI = 0.50–0.83; p = 0.001), CCL5 (OR = 0.57, CI = 0.39–0.83; p = 0.003), IRF9 (OR = 0.80, CI = 0.653–0.979; p = 0.03), and IFI6 (OR = 0.827, CI = 0.69–0.991; p = 0.039) expression was associated with patient survival. In conclusion, the relevance of OAS1, IRF9, and IFI6 in controlling the viral infection was confirmed. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

16 pages, 6389 KiB

Open AccessArticle

DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection

by Pihai Gong, Rongxin Zhang, Ke Xiao, Huiling Shu, Xinxiu Li, Hong Fan and Xiao Sun

Int. J. Mol. Sci. 2024, 25(8), 4422; https://doi.org/10.3390/ijms25084422 - 17 Apr 2024

Viewed by 677

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to raise concerns worldwide. Numerous host factors involved in SARS-CoV-2 infection have been identified, but the regulatory mechanisms of these host factor remain unclear. Here, we report the role of G-quadruplexes (G4s) located in the host factor promoter region in SARS-CoV-2 infection. Using bioinformatics, biochemical, and biological assays, we provide evidence for the presence of G4 structures in the promoter regions of SARS-CoV-2 host factors NRP1. Specifically, we focus on two representative G4s in the NRP1 promoter and highlight its importance in SARS-CoV-2 pathogenesis. The presence of the G4 structure greatly increases NRP1 expression, facilitating SARS-CoV-2 entry into cells. Utilizing published single-cell RNA sequencing data obtained from simulated SARS-CoV-2 infection in human bronchial epithelial cells (HBECs), we found that ciliated cells with high levels of NRP1 are prominently targeted by the virus during infection. Furthermore, our study identifies E2F1 act as a transcription factor that binds to G4s. These findings uncover a previously unknown mechanism underlying SARS-CoV-2 infection and suggest that targeting G4 structures could be a potential strategy for COVID-19 prevention and treatment. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

18 pages, 1445 KiB

Open AccessArticle

Sandwich ELISA for the Quantification of Nucleocapsid Protein of SARS-CoV-2 Based on Polyclonal Antibodies from Two Different Species

by Maja Mladenovic Stokanic, Ana Simovic, Vesna Jovanovic, Mirjana Radomirovic, Bozidar Udovicki, Maja Krstic Ristivojevic, Teodora Djukic, Tamara Vasovic, Jelena Acimovic, Ljiljana Sabljic, Ivana Lukic, Ana Kovacevic, Danica Cujic, Marija Gnjatovic, Katarina Smiljanic, Marija Stojadinovic, Jelena Radosavljevic, Dragana Stanic-Vucinic, Marijana Stojanovic, Andreja Rajkovic and Tanja Cirkovic Velickovic Show full author list Hide full author list

Int. J. Mol. Sci. 2024, 25(1), 333; https://doi.org/10.3390/ijms25010333 - 26 Dec 2023

Viewed by 1098

Abstract

In this study, a cost-effective sandwich ELISA test, based on polyclonal antibodies, for routine quantification SARS-CoV-2 nucleocapsid (N) protein was developed. The recombinant N protein was produced and used for the production of mice and rabbit antisera. Polyclonal N protein-specific antibodies served as capture and detection antibodies. The prototype ELISA has LOD 0.93 ng/mL and LOQ 5.3 ng/mL, with a linear range of 1.52–48.83 ng/mL. N protein heat pretreatment (56 °C, 1 h) decreased, while pretreatment with 1% Triton X-100 increased analytical ELISA sensitivity. The diagnostic specificity of ELISA was 100% (95% CI, 91.19–100.00%) and sensitivity was 52.94% (95% CI, 35.13–70.22%) compared to rtRT-PCR (Ct < 40). Profoundly higher sensitivity was obtained using patient samples mostly containing Wuhan-similar variants (Wuhan, alpha, and delta), 62.50% (95% CI, 40.59 to 81.20%), in comparison to samples mostly containing Wuhan-distant variants (Omicron) 30.00% (6.67–65.25%). The developed product has relatively high diagnostic sensitivity in relation to its analytical sensitivity due to the usage of polyclonal antibodies from two species, providing a wide repertoire of antibodies against multiple N protein epitopes. Moreover, the fast, simple, and inexpensive production of polyclonal antibodies, as the most expensive assay components, would result in affordable antigen tests. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

11 pages, 8596 KiB

Open AccessArticle

COVID-19 in Children: Molecular Profile and Pathological Features

by Ruslan A. Nasyrov, Dmitry O. Ivanov, Olga L. Krasnogorskaya, Vladimir N. Timchenko, Elena P. Fedotova, Alexander S. Chepelev, Veronika A. Galichina, Nadezhda A. Sidorova and Nikolai M. Anichkov

Int. J. Mol. Sci. 2023, 24(23), 16750; https://doi.org/10.3390/ijms242316750 - 25 Nov 2023

Viewed by 2265

Abstract

Although the World Health Organization has declared the end of the COVID-19 pandemic, doctors continue to register new cases of the disease among both adults and children. Unfortunately, the course of COVID-19 in children can have a severe form, with death being a potential outcome. The absence of published works discussing the pathological morphology of COVID-19 in children prevents the objective analysis of the disease’s pathogenesis, including among the adult population. In this vein, the objective of our study is to identify the morphological features of the lungs’ involvement and evaluate virus–host interactions in the case of COVID-19 in patients at a pediatric medical practice. We present the results of the study of the lungs of three children who died due to COVID-19, highlighting the predominant involvement of their respiratory organs at different stages of the disease (5, 21, and 50 days). This article presents data obtained from histopathological and immunohistochemical investigations, taking into account the results of clinical and laboratory indicators and intravital and postmortem SARS-CoV-2 PCR investigations. The common finding of all of the examined COVID-19 cases is the involvement of the endothelium in microcirculation vessels, which are considered to be a primary target of various pathogenic influencing factors. We also discuss both the significance of apoptosis as a result of virus–host interactions and the most likely cause of endothelium cell destruction. The results of this study could be useful for the development of endothelium-protective therapy to prevent the progression of disseminated intravascular coagulation syndrome. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

12 pages, 292 KiB

Open AccessArticle

Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome

by David Varillas-Delgado, Carmen Jimenez-Antona, Angel Lizcano-Alvarez, Roberto Cano-de-la-Cuerda, Alberto Molero-Sanchez and Sofia Laguarta-Val

Int. J. Mol. Sci. 2023, 24(23), 16717; https://doi.org/10.3390/ijms242316717 - 24 Nov 2023

Viewed by 1067

Abstract

Long COVID-19 syndrome is present in 5–10% of patients infected with SARS-CoV-2, and there is still little information on the predisposing factors that lead to its development. The purpose of the study was to evaluate the predictive factors in early symptoms, clinical features and the role of Angiotensin-Converting Enzyme-2 (ACE-2) c.513-1451G>A (rs2106806) and c.15643279T>C (rs6629110) polymorphisms in the susceptibility to developing Long COVID-19 syndrome subsequent to COVID-19 infectionA total of 29 patients who suffered COVID-19 were recruited in a descriptive longitudinal study of two groups: Long COVID-19 (n = 16) and non-Long COVID-19 (n = 13). Early symptoms and clinical features during COVID-19 were classified by a medical service. ACE-2 polymorphisms were genotyped by using a Single Nucleotide Primer Extension (SNPE). Of the early symptoms, fatigue, myalgia and headache showed a high risk of increasing Long COVID-19 susceptibility. Clinical features such as emergency care, SARS-CoV-2 reinfection, previous diseases, respiratory disease and brain fog also had a high risk of increasing Long COVID-19 susceptibility. The A allele in the rs2106806 variant was associated with an odds ratio (OR) of 4.214 (95% CI 2.521–8.853; p < 0.001), and the T allele in the rs6629110 variant was associated with an OR of 3.754 (95% CI 1.785–6.105; p = 0.002) of increasing Long COVID-19 susceptibility. This study shows the risk of ACE-2 polymorphisms, different early symptoms and clinical features during SARS-CoV-2 infection in susceptibility to Long COVID-19. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

15 pages, 4987 KiB

Open AccessArticle

Short Survey on the Protein Modifications in Plasma during SARS-CoV-2 Infection

by Agnieszka Gęgotek, Neven Zarkovic, Biserka Orehovec, Morana Jaganjac, Suzana Borovic Sunjic and Elżbieta Skrzydlewska

Int. J. Mol. Sci. 2023, 24(18), 14109; https://doi.org/10.3390/ijms241814109 - 14 Sep 2023

Cited by 2 | Viewed by 1094

Abstract

Although the COVID-19 pandemic has ended, it is important to understand the pathology of severe SARS-CoV-2 infection associated with respiratory failure and high mortality. The plasma proteome, including protein modification by lipid peroxidation products in COVID-19 survivors (COVID-19; n = 10) and deceased individuals (CovDeath; n = 10) was compared in samples collected upon admission to the hospital, when there was no difference in their status, with that of healthy individuals (Ctr; n = 10). The obtained results show that COVID-19 development strongly alters the expression of proteins involved in the regulation of exocytosis and platelet degranulation (top 20 altered proteins indicated by analysis of variance; p-value (False Discovery Rate) cutoff at 5%). These changes were most pronounced in the CovDeath group. In addition, the levels of 4-hydroxynonenal (4-HNE) adducts increased 2- and 3-fold, whereas malondialdehyde (MDA) adducts increased 7- and 2.5-fold, respectively, in COVID-19 and CovDeath groups. Kinases and proinflammatory proteins were particularly affected by these modifications. Protein adducts with 15-deoxy-12,14-prostaglandin J2 (15d-PGJ2) were increased 2.5-fold in COVID-19 patients, including modifications of proteins such as p53 and STAT3, whereas CovDeath showed a decrease of approximately 60% compared with Ctr. This study for the first time demonstrates the formation of lipid metabolism products—protein adducts in plasma from survived and deceased COVID-19 patients, significantly distinguishing them, which may be a predictor of the course of SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

17 pages, 1703 KiB

Open AccessArticle

Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients

by Elżbieta Skrzydlewska, Wojciech Łuczaj, Michał Biernacki, Piotr Wójcik, Iwona Jarocka-Karpowicz, Biserka Orehovec, Bruno Baršić, Marko Tarle, Marta Kmet, Ivica Lukšić, Zlatko Marušić, Georg Bauer and Neven Žarković

Int. J. Mol. Sci. 2023, 24(17), 13574; https://doi.org/10.3390/ijms241713574 - 1 Sep 2023

Viewed by 981

Abstract

The aim of this study was to evaluate selected parameters of redox signaling and inflammation in the granulocytes of COVID-19 patients who recovered and those who died. Upon admission, the patients did not differ in terms of any relevant clinical parameter apart from the percentage of granulocytes, which was 6% higher on average in those patients who died. Granulocytes were isolated from the blood of 15 healthy people and survivors and 15 patients who died within a week, and who were selected post hoc for analysis according to their matching gender and age. They differed only in the lethal outcome, which could not be predicted upon arrival at the hospital. The proteins level (respective ELISA), antioxidant activity (spectrophotometry), and lipid mediators (UPUPLC–MS) were measured in the peripheral blood granulocytes obtained via gradient centrifugation. The levels of Nrf2, HO-1, NFκB, and IL-6 were higher in the granulocytes of COVID-19 patients who died within a week, while the activity of cytoplasmic Cu,Zn-SOD and mitochondrial Mn-SOD and IL-2/IL-10 were lower in comparison to the levels observed in survivors. Furthermore, in the granulocytes of those patients who died, an increase in pro-inflammatory eicosanoids (PGE2 and TXB2), together with elevated cannabinoid receptors 1 and 2 (associated with a decrease in the anti-inflammatory 15d-PGJ2), were found. Hence, this study suggests that by triggering transcription factors, granulocytes activate inflammatory and redox signaling, leading to the production of pro-inflammatory eicosanoids while reducing cellular antioxidant capacity through SOD, thus expressing an altered response to COVID-19, which may result in the onset of systemic oxidative stress, ARDS, and the death of the patient. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

14 pages, 2511 KiB

Open AccessArticle

Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19

by Andrey Matveev, Oleg Pyankov, Yana Khlusevich, Olga Tyazhelkova, Lyudmila Emelyanova, Anna Timofeeva, Andrey Shipovalov, Anton Chechushkov, Natalia Zaitseva, Gleb Kudrov, Gaukhar Yusubalieva, Saule Yussubaliyeva, Oxana Zhukova, Vladimir Baklaushev, Sergey Sedykh, Galina Lifshits, Artem Tikunov and Nina Tikunova

Int. J. Mol. Sci. 2023, 24(13), 10799; https://doi.org/10.3390/ijms241310799 - 28 Jun 2023

Viewed by 2724

Abstract

Antibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hybridoma technology. mAb RS2 demonstrated sub-nanomolar affinity and ability to neutralize SARS-CoV-2 infection in vitro with IC₅₀ 360 ng/mL. In an animal model of SARS-CoV-2 infection, the dose-dependent protective efficacy of mAb RS2 was revealed. However, in post-exposure prophylaxis, the administration of mAb RS2 led to an increase in the viral load in the respiratory tract of animals. Three groups of blood plasma were examined for antibodies competing with mAb RS2: (1) plasmas from vaccinated donors without COVID-19; (2) plasmas from volunteers with mild symptoms of COVID-19; (3) plasmas from patients with severe COVID-19. It was demonstrated that antibodies competing with mAb RS2 were significantly more often recorded in sera from volunteers with severe COVID-19. The results demonstrated for the first time that in animals, SARS-CoV-2 can induce antibody/antibodies that can elicit ADE. Moreover, in the sera of patients with severe COVID-19, there are antibodies competing for the binding of an epitope that is recognized by the ADE-eliciting mAb. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

16 pages, 7368 KiB

Open AccessArticle

High Expression Levels of miR-21-5p in Younger Hospitalized COVID-19 Patients Are Associated with Mortality and Critical Disease

by Brandon Bautista-Becerril, Karol J. Nava-Quiroz, Evangelina Muñoz-Soria, Ángel Camarena, Ingrid Fricke-Galindo, Ivette Buendia-Roldan, Gloria Pérez-Rubio, Leslie Chavez-Galán, Karina Pérez-Torres, Fernanda Téllez-Quijada, Eduardo Márquez-García, Angelica Moncada-Morales, Rafael de Jesús Hernández-Zenteno, María Esther Jaime-Capetillo and Ramcés Falfán-Valencia

Int. J. Mol. Sci. 2023, 24(12), 10112; https://doi.org/10.3390/ijms241210112 - 14 Jun 2023

Cited by 1 | Viewed by 1733

Abstract

In COVID-19, critical disease and invasive mechanical ventilation (IMV) increase the risk of death, mainly in patients over 60 years of age. Objectives: To find the relationship between miR-21-5p and miR-146a-5p in terms of the severity, IMV, and mortality in hospitalized COVID-19 patients younger than 55 years of age. Methods: The patients were stratified according to disease severity using the IDSA/WHO criteria for severe and critical COVID-19 and subclassified into critical non-survivors and critical survivors. Results: Ninety-seven severe/critical COVID-19 patients were included; 81.3% of the deceased were male and 18.8% were female. Higher expression miR-21-5p levels were associated as follows: severe vs. critical disease (p = 0.007, FC = 0.498), PaO₂/FiO₂ index, mild vs. severe (p = 0.027, FC = 0.558), and survivors vs. non-survivors (p = 0.03, FC = 0.463). Moreover, we identified correlations with clinical variables: CRP (rho = −0.54, p < 0.001), D-dimer (rho = −0.47, p < 0.05), related to damage in the kidney (rho = 0.60, p < 0.001), liver (rho = 0.41, p < 0.05), and lung (rho = 0.54, p < 0.001). Finally, miR-21-5p thresholds were calculated according to severity (8.191), IMV (8.191), and mortality (8.237); these values increased the risk of developing a critical disease (OR = 4.19), the need for IMV (OR = 5.63), and death (OR = 6.00). Conclusion: Increased expression levels of miR-21-5p are related to worse outcome of COVID-19 in younger hospitalized patients. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

17 pages, 3968 KiB

Open AccessArticle

Comparative Analysis of a Human Neutralizing mAb Specific for SARS-CoV-2 Spike-RBD with Cilgavimab and Tixagevimab for the Efficacy on the Omicron Variant in Neutralizing and Detection Assays

by Margherita Passariello, Speranza Esposito, Lorenzo Manna, Rosa Rapuano Lembo, Immacolata Zollo, Emanuele Sasso, Felice Amato and Claudia De Lorenzo

Int. J. Mol. Sci. 2023, 24(12), 10053; https://doi.org/10.3390/ijms241210053 - 13 Jun 2023

Cited by 1 | Viewed by 1213

Abstract

The recent pandemic years have prompted the scientific community to increasingly search for and adopt new and more efficient therapeutic and diagnostic approaches to deal with a new infection. In addition to the development of vaccines, which has played a leading role in fighting the pandemic, the development of monoclonal antibodies has also represented a valid approach in the prevention and treatment of many cases of CoronaVirus Disease 2019 (COVID-19). Recently, we reported the development of a human antibody, named D3, showing neutralizing activity against different SARS-CoV-2 variants, wild-type, UK, Delta and Gamma variants. Here, we have further characterized with different methods D3’s ability to bind the Omicron-derived recombinant RBD by comparing it with the antibodies Cilgavimab and Tixagevimab, recently approved for prophylactic use of COVID-19. We demonstrate here that D3 binds to a distinct epitope from that recognized by Cilgavimab and shows a different binding kinetic behavior. Furthermore, we report that the ability of D3 to bind the recombinant Omicron RBD domain in vitro results in a good ability to also neutralize Omicron-pseudotyped virus infection in ACE2-expressing cell cultures. We point out here that D3 mAb maintains a good ability to recognize both the wild-type and Omicron Spike proteins, either when used as recombinant purified proteins or when expressed on pseudoviral particles despite the different variants, making it particularly useful both from a therapeutic and diagnostic point of view. On the basis of these results, we propose to exploit this mAb for combinatorial treatments with other neutralizing mAbs to increase their therapeutic efficacy and for diagnostic use to measure the viral load in biological samples in the current and future pandemic waves of coronaviruses. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

Review

Jump to: Research

17 pages, 1255 KiB

Open AccessReview

After the Hurricane: Anti-COVID-19 Drugs Development, Molecular Mechanisms of Action and Future Perspectives

by Hazim O. Khalifa and Yousef M. Al Ramahi

Int. J. Mol. Sci. 2024, 25(2), 739; https://doi.org/10.3390/ijms25020739 - 6 Jan 2024

Cited by 4 | Viewed by 1618

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a new coronavirus in the Coronaviridae family. The COVID-19 pandemic, caused by SARS-CoV-2, has undoubtedly been the largest crisis of the twenty-first century, resulting in over 6.8 million deaths and 686 million confirmed cases, creating a global public health issue. Hundreds of notable articles have been published since the onset of this pandemic to justify the cause of viral spread, viable preventive measures, and future therapeutic approaches. As a result, this review was developed to provide a summary of the current anti-COVID-19 drugs, as well as their timeline, molecular mode of action, and efficacy. It also sheds light on potential future treatment options. Several medications, notably hydroxychloroquine and lopinavir/ritonavir, were initially claimed to be effective in the treatment of SARS-CoV-2 but eventually demonstrated inadequate activity, and the Food and Drug Administration (FDA) withdrew hydroxychloroquine. Clinical trials and investigations, on the other hand, have demonstrated the efficacy of remdesivir, convalescent plasma, and monoclonal antibodies, 6-Thioguanine, hepatitis C protease inhibitors, and molnupiravir. Other therapeutics, including inhaled medicines, flavonoids, and aptamers, could pave the way for the creation of novel anti-COVID-19 therapies. As future pandemics are unavoidable, this article urges immediate action and extensive research efforts to develop potent specialized anti-COVID-19 medications. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

18 pages, 1324 KiB

Open AccessReview

Dynamics of the Microbiota and Its Relationship with Post-COVID-19 Syndrome

by Nidia Carolina Moreno-Corona, Orestes López-Ortega, Cesar Augusto Pérez-Martínez, Macario Martínez-Castillo, Luis Adrián De Jesús-González, Guadalupe León-Reyes and Moisés León-Juárez

Int. J. Mol. Sci. 2023, 24(19), 14822; https://doi.org/10.3390/ijms241914822 - 1 Oct 2023

Cited by 3 | Viewed by 1778

Abstract

Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies. Full article

(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Molecular Research and Insights into COVID-19

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (13 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI