International Journal of Molecular Sciences

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15 pages, 1997 KiB

Open AccessArticle

Nutritional and Inflammatory Markers Associated with SARS-CoV-2 Infection in the Elderly

by João Ismael Budelon Gonçalves, Fernanda Muller Lermen, Júlia Budelon Gonçalves, Gabriele Zanirati, Denise Cantarelli Machado, Helena Morsch Marques, Helena Scartassini Erwig, Bruno Maestri Becker, Fernanda Wagner, Marina Ottmann Boff, Murilo Gomes Rocha, Jaderson Costa Da Costa and e Daniel Marinowic

Int. J. Mol. Sci. 2024, 25(14), 7749; https://doi.org/10.3390/ijms25147749 - 15 Jul 2024

Viewed by 879

Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented challenges to global health systems, particularly among vulnerable populations such as the elderly. Understanding the interplay between anthropometric markers, molecular profiles, and disease severity is crucial for effective clinical management and intervention [...] Read more.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented challenges to global health systems, particularly among vulnerable populations such as the elderly. Understanding the interplay between anthropometric markers, molecular profiles, and disease severity is crucial for effective clinical management and intervention strategies. We conducted a cohort study comprising 43 elderly COVID-19 patients admitted to São Lucas Hospital, PUCRS, Brazil. Anthropometric measurements, including calf circumference (CC) and abdominal circumference (AC), were assessed alongside molecular analyses of peripheral blood samples obtained within 48 h of hospital admission. Sociodemographic data were collected from electronic medical records for comprehensive analysis. Our findings revealed a possible relationship between overweight status, increased abdominal adiposity, and prolonged hospitalization duration, alongside heightened disease severity. We also found no significant correlations between BMI, vitamin D levels, and clinical outcomes. Elevated oxygen requirements were observed in both normal and overweight individuals, with the latter necessitating prolonged oxygen therapy. Molecular analyses revealed changes in the inflammatory profile regarding the outcome of the patients. Our study highlights the critical importance of both anthropometric and molecular markers in predicting disease severity and clinical outcomes in elderly individuals with COVID-19. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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18 pages, 6537 KiB

Open AccessArticle

A Receptor Integrin β1 Promotes Infection of Avian Metapneumovirus Subgroup C by Recognizing a Viral Fusion Protein RSD Motif

by Yongqiu Cui, Siting Li, Weiyin Xu, Yeqiu Li, Jiali Xie, Dedong Wang, Jinshuo Guo, Jianwei Zhou, Xufei Feng, Lei Hou and Jue Liu

Int. J. Mol. Sci. 2024, 25(2), 829; https://doi.org/10.3390/ijms25020829 - 9 Jan 2024

Cited by 1 | Viewed by 1528

Abstract

Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin β1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. [...] Read more.

Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin β1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. Herein, we demonstrate that ITGB1 is essential for aMPV/C infection in cultured DF-1 cells, as evidenced by the inhibition of viral binding by EDTA blockade, Arg-Ser-Asp (RSD) peptide, monoclonal antibody against ITGB1, and ITGB1 short interfering (si) RNA knockdown in cultured DF-1 cells. Simulation of the binding process between the aMPV/C fusion (F) protein and avian-derived ITGB1 using molecular dynamics showed that ITGB1 may be a host factor benefiting aMPV/C attachment or internalization. The transient expression of avian ITGB1-rendered porcine and feline non-permissive cells (DQ cells and CRFK cells, respectively) is susceptible to aMPV/C infection. Kinetic replication of aMPV/C in siRNA-knockdown cells revealed that ITGB1 plays an important role in aMPV/C infection at the early stage (attachment and internalization). aMPV/C was also able to efficiently infect human non-small cell lung cancer (A549) cells. This may be a consequence of the similar structures of both metapneumovirus F protein-specific motifs (RSD for aMPV/C and RGD for human metapneumovirus) recognized by ITGB1. Overexpression of avian-derived ITGB1 and human-derived ITGB1 in A549 cells enhanced aMPV/C infectivity. Taken together, this study demonstrated that ITGB1 acts as an essential receptor for aMPV/C attachment and internalization into host cells, facilitating aMPV/C infection. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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12 pages, 2992 KiB

Open AccessArticle

The Modification of the Illumina^® CovidSeq™ Workflow for RSV Genomic Surveillance: The Genetic Variability of RSV during the 2022–2023 Season in Northwest Spain

by Carlos Davina-Nunez, Sonia Perez-Castro, Jorge Julio Cabrera-Alvargonzalez, Jhon Montano-Barrientos, Montse Godoy-Diz and Benito Regueiro

Int. J. Mol. Sci. 2023, 24(22), 16055; https://doi.org/10.3390/ijms242216055 - 7 Nov 2023

Cited by 2 | Viewed by 1930

Abstract

There is growing interest in the molecular surveillance of the Respiratory Syncytial Virus and the monitorization of emerging mutations that could impair the efficacy of antiviral prophylaxis and treatments. A simple, scalable protocol for viral nucleic acid enrichment could improve the surveillance of [...] Read more.

There is growing interest in the molecular surveillance of the Respiratory Syncytial Virus and the monitorization of emerging mutations that could impair the efficacy of antiviral prophylaxis and treatments. A simple, scalable protocol for viral nucleic acid enrichment could improve the surveillance of RSV. We developed a protocol for RSV-A and B amplification based on the Illumina CovidSeq workflow using an RSV primer panel. A total of 135 viral genomes were sequenced from nasopharyngeal samples through the optimization steps of this panel, while an additional 15 samples were used to test the final version. Full coverage of the G gene and over 95% of the coverage of the F gene, the target of the available RSV antivirals or monoclonal antibodies, were obtained. The F:K68N mutation, associated with decreased nirsevimab activity, was detected in our facility. Additionally, phylogenetic analysis showed several sublineages in the 2022–2023 influenza season in Europe. Our protocol allows for a simple and scalable simultaneous amplification of the RSV-A and B whole genome, increasing the yield of RSV sequencing and reducing costs. Its application would allow the world to be ready for the detection of arising mutations in relation to the widespread use of nirsevimab for RSV prevention. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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17 pages, 2448 KiB

Open AccessArticle

Pseudotyping Improves the Yield of Functional SARS-CoV-2 Virus-like Particles (VLPs) as Tools for Vaccine and Therapeutic Development

by Andrew J. Zak, Trang Hoang, Christine M. Yee, Syed M. Rizvi, Ponnandy Prabhu and Fei Wen

Int. J. Mol. Sci. 2023, 24(19), 14622; https://doi.org/10.3390/ijms241914622 - 27 Sep 2023

Viewed by 1694

Abstract

Virus-like particles (VLPs) have been proposed as an attractive tool in SARS-CoV-2 vaccine development, both as (1) a vaccine candidate with high immunogenicity and low reactogenicity and (2) a substitute for live virus in functional and neutralization assays. Though multiple SARS-CoV-2 VLP designs [...] Read more.

Virus-like particles (VLPs) have been proposed as an attractive tool in SARS-CoV-2 vaccine development, both as (1) a vaccine candidate with high immunogenicity and low reactogenicity and (2) a substitute for live virus in functional and neutralization assays. Though multiple SARS-CoV-2 VLP designs have already been explored in Sf9 insect cells, a key parameter ensuring VLPs are a viable platform is the VLP spike yield (i.e., spike protein content in VLP), which has largely been unreported. In this study, we show that the common strategy of producing SARS-CoV-2 VLPs by expressing spike protein in combination with the native coronavirus membrane and/or envelope protein forms VLPs, but at a critically low spike yield (~0.04–0.08 mg/L). In contrast, fusing the spike ectodomain to the influenza HA transmembrane domain and cytoplasmic tail and co-expressing M1 increased VLP spike yield to ~0.4 mg/L. More importantly, this increased yield translated to a greater VLP spike antigen density (~96 spike monomers/VLP) that more closely resembles that of native SARS-CoV-2 virus (~72–144 Spike monomers/virion). Pseudotyping further allowed for production of functional alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) SARS-CoV-2 VLPs that bound to the target ACE2 receptor. Finally, we demonstrated the utility of pseudotyped VLPs to test neutralizing antibody activity using a simple, acellular ELISA-based assay performed at biosafety level 1 (BSL-1). Taken together, this study highlights the advantage of pseudotyping over native SARS-CoV-2 VLP designs in achieving higher VLP spike yield and demonstrates the usefulness of pseudotyped VLPs as a surrogate for live virus in vaccine and therapeutic development against SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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8 pages, 700 KiB

Open AccessCommunication

Performance of Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) Targeting the RNA Polymerase Gene for the Direct Detection of SARS-CoV2 in Nasopharyngeal Swabs

by Elias da Rosa Hoffmann, Lisiane da Rocha Balzan, Everton Inamine, Lisiane Rech Pancotto, Guilherme Gaboardi and Vlademir Vicente Cantarelli

Int. J. Mol. Sci. 2023, 24(17), 13056; https://doi.org/10.3390/ijms241713056 - 22 Aug 2023

Cited by 1 | Viewed by 1261

Abstract

In 2020, a global pandemic caused by SARS-CoV-2 was declared. Different institutes proposed diagnostic molecular methods to detect the virus in clinical samples. This study aims to validate and standardize the use of a loop-mediated isothermal amplification (LAMP)-based methodology targeting the viral RP [...] Read more.

In 2020, a global pandemic caused by SARS-CoV-2 was declared. Different institutes proposed diagnostic molecular methods to detect the virus in clinical samples. This study aims to validate and standardize the use of a loop-mediated isothermal amplification (LAMP)-based methodology targeting the viral RP gene, as a faster and low-cost diagnostic method for SARS-CoV-2 infections. The results obtained with RT-LAMP (Reverse Transcriptase) were compared to the results of real-time polymerase chain reaction (RT-PCR) to assess its sensitivity and specificity. In total, 115 samples (nasopharyngeal samples) were used for detecting SARS-CoV-2 by RT-LAMP, with 43 positives and 72 negatives. The study showed a positive predictive value (PPV) of 90.7% and a negative predictive value (VPN) of 100%. The LAMP assay also demonstrated a high sensitivity of 90.7% and a specificity of 100% (confidence interval 77.9–97.4%) when using the lower detection limit of 40 copies/µL. The RT-LAMP described here has the potential to detect even the new variants of SARS-CoV-2, suggesting that it may not be significantly affected by gene mutations. The RT-LAMP targeting the RP viral region is faster and less expensive than other molecular approaches, making it an alternative for developing countries. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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14 pages, 4677 KiB

Open AccessArticle

PEMT Mediates Hepatitis C Virus-Induced Steatosis, Explains Genotype-Specific Phenotypes and Supports Virus Replication

by Mosleh Abomughaid, Enoch S. E. Tay, Russell Pickford, Chandra Malladi, Scott A. Read, Jens R. Coorssen, Brian S. Gloss, Jacob George and Mark W. Douglas

Int. J. Mol. Sci. 2023, 24(10), 8781; https://doi.org/10.3390/ijms24108781 - 15 May 2023

Cited by 4 | Viewed by 2039

Abstract

The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, [...] Read more.

The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline (p < 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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Review

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32 pages, 4753 KiB

Open AccessReview

Breaking the Chain: Protease Inhibitors as Game Changers in Respiratory Viruses Management

by Christos Papaneophytou

Int. J. Mol. Sci. 2024, 25(15), 8105; https://doi.org/10.3390/ijms25158105 - 25 Jul 2024

Viewed by 1420

Abstract

Respiratory viral infections (VRTIs) rank among the leading causes of global morbidity and mortality, affecting millions of individuals each year across all age groups. These infections are caused by various pathogens, including rhinoviruses (RVs), adenoviruses (AdVs), and coronaviruses (CoVs), which are particularly prevalent [...] Read more.

Respiratory viral infections (VRTIs) rank among the leading causes of global morbidity and mortality, affecting millions of individuals each year across all age groups. These infections are caused by various pathogens, including rhinoviruses (RVs), adenoviruses (AdVs), and coronaviruses (CoVs), which are particularly prevalent during colder seasons. Although many VRTIs are self-limiting, their frequent recurrence and potential for severe health complications highlight the critical need for effective therapeutic strategies. Viral proteases are crucial for the maturation and replication of viruses, making them promising therapeutic targets. This review explores the pivotal role of viral proteases in the lifecycle of respiratory viruses and the development of protease inhibitors as a strategic response to these infections. Recent advances in antiviral therapy have highlighted the effectiveness of protease inhibitors in curtailing the spread and severity of viral diseases, especially during the ongoing COVID-19 pandemic. It also assesses the current efforts aimed at identifying and developing inhibitors targeting key proteases from major respiratory viruses, including human RVs, AdVs, and (severe acute respiratory syndrome coronavirus-2) SARS-CoV-2. Despite the recent identification of SARS-CoV-2, within the last five years, the scientific community has devoted considerable time and resources to investigate existing drugs and develop new inhibitors targeting the virus’s main protease. However, research efforts in identifying inhibitors of the proteases of RVs and AdVs are limited. Therefore, herein, it is proposed to utilize this knowledge to develop new inhibitors for the proteases of other viruses affecting the respiratory tract or to develop dual inhibitors. Finally, by detailing the mechanisms of action and therapeutic potentials of these inhibitors, this review aims to demonstrate their significant role in transforming the management of respiratory viral diseases and to offer insights into future research directions. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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20 pages, 1211 KiB

Open AccessReview

Antiviral Therapy of COVID-19

by Georgii Gudima, Ilya Kofiadi, Igor Shilovskiy, Dmitry Kudlay and Musa Khaitov

Int. J. Mol. Sci. 2023, 24(10), 8867; https://doi.org/10.3390/ijms24108867 - 16 May 2023

Cited by 18 | Viewed by 4892

Abstract

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased [...] Read more.

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19. Full article

(This article belongs to the Special Issue Molecular Research of Viral Infections)

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