Research

12 pages, 1480 KiB

Open AccessArticle

Interaction of Laurusides 1 and 2 with the 3C-like Protease (M^pro) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study

by Ida Autiero and Giovanni N. Roviello

Int. J. Mol. Sci. 2023, 24(6), 5511; https://doi.org/10.3390/ijms24065511 - 14 Mar 2023

Cited by 2 | Viewed by 1496

Abstract

Laurus nobilis (bay laurel) is a natural source of biological compounds, and some of its extracts and phytocompounds are also endowed with antiviral activity toward the family of the severe acute respiratory syndrome (SARS)-associated β-coronaviruses. Some glycosidic laurel compounds such as laurusides were [...] Read more.

Laurus nobilis (bay laurel) is a natural source of biological compounds, and some of its extracts and phytocompounds are also endowed with antiviral activity toward the family of the severe acute respiratory syndrome (SARS)-associated β-coronaviruses. Some glycosidic laurel compounds such as laurusides were proposed as inhibitors of important protein targets of SARS-CoV-2, which clearly recalls their potential as anti-COVID-19 drugs. Due to the frequent genomic variations of the β-coronaviruses and the consequent importance of evaluating a new drug candidate with respect to the variants of the target β-coronavirus, we decided to investigate at an atomistic level the molecular interactions of the potential laurel-derived drugs laurusides 1 and 2 (L01 and L02, respectively) toward a well-conserved and crucial target, the 3C-like protease (M^pro), using the enzymes of both the wild-type of SARS-CoV-2 and of the more recent Omicron variant. Thus, we performed molecular dynamic (MD) simulations of laurusides—SARS-CoV-2 protease complexes to deepen the knowledge on the stability of the interaction and compare the effects of the targeting among the two genomic variants. We found that the Omicron mutation does not significantly impact the lauruside binding and that L02 connects more stably with respect to L01 in the complexes from both variants, even though both compounds prevalently interact within the same binding pocket. Although purely in silico, the current study highlights the potential role of bay laurel phytocompounds in the antiviral and specifically anti-coronavirus research and shows their potential binding toward M^pro, corroborating the important commitment of bay laurel as functional food and disclosing novel scenarios of lauruside-based antiviral therapies. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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16 pages, 2723 KiB

Open AccessArticle

Detection of the Omicron SARS-CoV-2 Lineage and Its BA.1 Variant with Multiplex RT-qPCR

by Nikita D. Yolshin, Andrey B. Komissarov, Kirill V. Varchenko, Tamila D. Musaeva, Artem V. Fadeev and Dmitry A. Lioznov

Int. J. Mol. Sci. 2022, 23(24), 16153; https://doi.org/10.3390/ijms232416153 - 18 Dec 2022

Cited by 3 | Viewed by 1615

Abstract

Whole genome sequencing (WGS) is considered the best instrument to track both virus evolution and the spread of new, emerging variants. However, WGS still does not allow the analysis of as many samples as qPCR does. Epidemiological and clinical research needs to develop [...] Read more.

Whole genome sequencing (WGS) is considered the best instrument to track both virus evolution and the spread of new, emerging variants. However, WGS still does not allow the analysis of as many samples as qPCR does. Epidemiological and clinical research needs to develop advanced qPCR methods to identify emerging variants of SARS-CoV-2 while collecting data on their spreading in a faster and cheaper way, which is critical for introducing public health measures. This study aimed at designing a one-step RT-qPCR assay for multiplex detection of the Omicron lineage and providing additional data on its subvariants in clinical samples. The RT-qPCR assay demonstrated high sensitivity and specificity on multiple SARS-CoV-2 variants and was cross-validated by WGS. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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12 pages, 2959 KiB

Open AccessArticle

Genetic and Structural Data on the SARS-CoV-2 Omicron BQ.1 Variant Reveal Its Low Potential for Epidemiological Expansion

by Fabio Scarpa, Daria Sanna, Domenico Benvenuto, Alessandra Borsetti, Ilenia Azzena, Marco Casu, Pier Luigi Fiori, Marta Giovanetti, Antonello Maruotti, Giancarlo Ceccarelli, Arnaldo Caruso, Francesca Caccuri, Roberto Cauda, Antonio Cassone, Stefano Pascarella and Massimo Ciccozzi

Int. J. Mol. Sci. 2022, 23(23), 15264; https://doi.org/10.3390/ijms232315264 - 03 Dec 2022

Cited by 14 | Viewed by 2433

Abstract

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating [...] Read more.

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10⁻⁴ and 7 × 10⁻⁴ subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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14 pages, 2192 KiB

Open AccessArticle

Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH

by Eeva Tortellini, Maria Antonella Zingaropoli, Giulia Mancarella, Raffaella Marocco, Anna Carraro, Meriem Jamhour, Christian Barbato, Mariasilvia Guardiani, Federica Dominelli, Patrizia Pasculli, Anna Napoli, Aurelia Gaeta, Fabio Mengoni, Paola Zuccalà, Valeria Belvisi, Blerta Kertusha, Alberico Parente, Cosmo Del Borgo, Vincenzo Vullo, Maria Rosa Ciardi, Claudio Maria Mastroianni, Miriam Lichtner and LATINA COVID-19 Group Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(23), 14988; https://doi.org/10.3390/ijms232314988 - 30 Nov 2022

Cited by 8 | Viewed by 1889

Abstract

We investigated specific humoral and T-cell responses in people living with HIV (PLWH) before (T0), after two (T1) and after six months (T2) from the third dose of the BNT162b2 vaccine. Healthy donors (HD) were enrolled. The specific humoral response was present in [...] Read more.

We investigated specific humoral and T-cell responses in people living with HIV (PLWH) before (T0), after two (T1) and after six months (T2) from the third dose of the BNT162b2 vaccine. Healthy donors (HD) were enrolled. The specific humoral response was present in most PLWH already after the second dose, but the third dose increased both the rate of response and its magnitude. Collectively, no significant differences were found in the percentage of responding T-cells between PLWH and HD. At T0, stratifying PLWH according to CD4 cell count, a lower percentage of responding T-cells in <200 cells/µL subgroup compared to >200 cells/µL one was observed. At T1, this parameter was comparable between the two subgroups, and the same result was found at T2. However, the pattern of co-expression of IFNγ, IL2 and TNFα in PLWH was characterized by a higher expression of TNFα, independently of CD4 cell count, indicating a persistent immunological signature despite successful ART. mRNA vaccination elicited a specific response in most PLWH, although the cellular one seems qualitatively inferior compared to HD. Therefore, an understanding of the T-cell quality dynamic is needed to determine the best vaccination strategy and, in general, the capability of immune response in ART-treated PLWH. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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16 pages, 2854 KiB

Open AccessArticle

Dynamics of SARS-CoV-2 Major Genetic Lineages in Moscow in the Context of Vaccine Prophylaxis

by Vladimir A. Gushchin, Andrei A. Pochtovyi, Daria D. Kustova, Darya A. Ogarkova, Ivan Y. Tarnovetskii, Elizaveta D. Belyaeva, Elizaveta V. Divisenko, Lyudmila A. Vasilchenko, Elena V. Shidlovskaya, Nadezhda A. Kuznetsova, Artem P. Tkachuk, Egor A. Slutskiy, Gleb I. Speshilov, Andrei G. Komarov, Alexander N. Tsibin, Vladimir I. Zlobin, Denis Y. Logunov and Alexander L. Gintsburg

Int. J. Mol. Sci. 2022, 23(23), 14670; https://doi.org/10.3390/ijms232314670 - 24 Nov 2022

Cited by 8 | Viewed by 1723

Abstract

Findings collected over two and a half years of the COVID-19 pandemic demonstrated that the level immunity resulting from vaccination and infection is insufficient to stop the circulation of new genetic variants. The short-term decline in morbidity was followed by a steady increase. [...] Read more.

Findings collected over two and a half years of the COVID-19 pandemic demonstrated that the level immunity resulting from vaccination and infection is insufficient to stop the circulation of new genetic variants. The short-term decline in morbidity was followed by a steady increase. The early identification of new genetic lineages that will require vaccine adaptation in the future is an important research target. In this study, we summarised data on the variability of genetic line composition throughout the COVID-19 pandemic in Moscow, Russia, and evaluated the virological and epidemiological features of dominant variants in the context of selected vaccine prophylaxes. The prevalence of the Omicron variant highlighted the low effectiveness of the existing immune layer in preventing infection, which points to the necessity of optimising the antigens used in vaccines in Moscow. Logistic growth curves showing the rate at which the new variant displaces the previously dominant variants may serve as early indicators for selecting candidates for updated vaccines, along with estimates of efficacy, reduced viral neutralising activity against the new strains, and viral load in previously vaccinated patients. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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14 pages, 3474 KiB

Open AccessArticle

The Spike Mutants Website: A Worldwide Used Resource against SARS-CoV-2

by Isabella Romeo, Ingrid Guarnetti Prandi, Emanuela Giombini, Cesare Ernesto Maria Gruber, Daniele Pietrucci, Stefano Borocci, Nabil Abid, Anna Fava, Andrea R. Beccari, Giovanni Chillemi and Carmine Talarico

Int. J. Mol. Sci. 2022, 23(21), 13082; https://doi.org/10.3390/ijms232113082 - 28 Oct 2022

Cited by 6 | Viewed by 1540

Abstract

A large number of SARS-CoV-2 mutations in a short period of time has driven scientific research related to vaccines, new drugs, and antibodies to combat the new variants of the virus. Herein, we present a web portal containing the structural information, the tridimensional [...] Read more.

A large number of SARS-CoV-2 mutations in a short period of time has driven scientific research related to vaccines, new drugs, and antibodies to combat the new variants of the virus. Herein, we present a web portal containing the structural information, the tridimensional coordinates, and the molecular dynamics trajectories of the SARS-CoV-2 spike protein and its main variants. The Spike Mutants website can serve as a rapid online tool for investigating the impact of novel mutations on virus fitness. Taking into account the high variability of SARS-CoV-2, this application can help the scientific community when prioritizing molecules for experimental assays, thus, accelerating the identification of promising drug candidates for COVID-19 treatment. Below we describe the main features of the platform and illustrate the possible applications for speeding up the drug discovery process and hypothesize new effective strategies to overcome the recurrent mutations in SARS-CoV-2 genome. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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14 pages, 1578 KiB

Open AccessArticle

SARS-CoV-2 Spatiotemporal Genomic and Molecular Analysis of the First Wave of the COVID-19 Pandemic in Macaé, the Brazilian Capital of Oil

by Bruno da-Costa-Rodrigues, Caio Cheohen, Felipe Sciammarella, Allan Pierre-Bonetti-Pozzobon, Lupis Ribeiro, José Luciano Nepomuceno-Silva, Marcio Medeiros, Flávia Mury, Cintia Monteiro-de-Barros, Cristiano Lazoski, Manuela Leal-da-Silva, Amilcar Tanuri and Rodrigo Nunes-da-Fonseca

Int. J. Mol. Sci. 2022, 23(19), 11497; https://doi.org/10.3390/ijms231911497 - 29 Sep 2022

Cited by 1 | Viewed by 1546

Abstract

The SARS-CoV-2 virus infection led to millions of deaths during the COVID-19 pandemic. Hundreds of workers from several other Brazilian cities, as well as from other countries, arrive daily in Macaé to work in the oil supply chain, making this city a putative [...] Read more.

The SARS-CoV-2 virus infection led to millions of deaths during the COVID-19 pandemic. Hundreds of workers from several other Brazilian cities, as well as from other countries, arrive daily in Macaé to work in the oil supply chain, making this city a putative hotspot for the introduction of new viral lineages. In this study, we performed a genomic survey of SARS-CoV-2 samples from Macaé during the first outbreak of COVID-19, combined with clinical data and a molecular integrative analysis. First, phylogenomic analyses showed a high occurrence of viral introduction events and the establishment of local transmissions in Macaé, including the ingression and spread of the B.1.1.28 lineage in the municipality from June to August 2020. Second, SARS-CoV-2 mutations were identified in patients with distinct levels of COVID-19 severity. Third, molecular interactions of the mutated spike protein from three B.1.1.33 local samples and human ACE2 showed higher interactions than that of the wild-type spike protein from the ancestral virus. Altogether, these results elucidate the SARS-CoV-2 genomic profile in a strategic Brazilian city and further explore the functional aspects of SARS-CoV-2 with a characterization of emerging viral mutations associated with clinical data and the potential targets for drug development against SARS-CoV-2. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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12 pages, 626 KiB

Open AccessArticle

Differentiation of SARS-CoV-2 Variants Using RT-qPCRs by Targeting Recurrent Mutation Sites: A Diagnostic Laboratory Experience from Multi-Center Regional Study, August 2020–December 2021, Poland

by Karolina Wegrzynska, Magdalena Komiazyk, Jaroslaw Walory, Aleksandra Kozinska, Izabela Wasko and Anna Baraniak

Int. J. Mol. Sci. 2022, 23(16), 9416; https://doi.org/10.3390/ijms23169416 - 20 Aug 2022

Cited by 8 | Viewed by 1915

Abstract

Rapid identification of SARS-CoV-2 variants is essential for epidemiological surveillance. RT-qPCR-based variant differentiation tests can be used to quickly screen large sets of samples for relevant variants of concern/interest; this study was conducted on specimens collected at 11 centers located in Poland during [...] Read more.

Rapid identification of SARS-CoV-2 variants is essential for epidemiological surveillance. RT-qPCR-based variant differentiation tests can be used to quickly screen large sets of samples for relevant variants of concern/interest; this study was conducted on specimens collected at 11 centers located in Poland during routine SARS-CoV-2 diagnostics between August 2020 and December 2021. A total of 1096 samples (with CT < 30) were screened for Alpha, Beta, Delta, Kappa and Omicron variants using commercial assays targeting repeat mutation sites. Variants were assigned to 434 (39.6%) specimens; the remaining 662 (60.4%) samples were not classified (no tested mutations detected). Alpha (n = 289; 66.59%), Delta (n = 115; 26.5%), Kappa (n = 30; 6.91%) and Omicron (n = 2; 0.46%) variants were identified and their distribution changed over time. The first Alpha variant appeared in October 2020, and it began to gradually increase its proportion of the virus population by June 2021. In July 2021, it was replaced by the Delta variant, which already dominated by the end of the year. The first Kappa was detected in October 2021, while Omicron was found in December 2021. The screening of samples allowed the determination of epidemiological trends over a time interval reflecting the national COVID-19 waves. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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18 pages, 8782 KiB

Open AccessArticle

Structural Evolution of Delta (B.1.617.2) and Omicron (BA.1) Spike Glycoproteins

by Ingrid Guarnetti Prandi, Carla Mavian, Emanuela Giombini, Cesare E. M. Gruber, Daniele Pietrucci, Stefano Borocci, Nabil Abid, Andrea R. Beccari, Carmine Talarico and Giovanni Chillemi

Int. J. Mol. Sci. 2022, 23(15), 8680; https://doi.org/10.3390/ijms23158680 - 04 Aug 2022

Cited by 7 | Viewed by 2070

Abstract

The vast amount of epidemiologic and genomic data that were gathered as a global response to the COVID-19 pandemic that was caused by SARS-CoV-2 offer a unique opportunity to shed light on the structural evolution of coronaviruses and in particular on the spike [...] Read more.

The vast amount of epidemiologic and genomic data that were gathered as a global response to the COVID-19 pandemic that was caused by SARS-CoV-2 offer a unique opportunity to shed light on the structural evolution of coronaviruses and in particular on the spike (S) glycoprotein, which mediates virus entry into the host cell by binding to the human ACE2 receptor. Herein, we carry out an investigation into the dynamic properties of the S glycoprotein, focusing on the much more transmissible Delta and Omicron variants. Notwithstanding the great number of mutations that have accumulated, particularly in the Omicron S glycoprotein, our data clearly showed the conservation of some structural and dynamic elements, such as the global motion of the receptor binding domain (RBD). However, our studies also revealed structural and dynamic alterations that were concentrated in the aa 627–635 region, on a small region of the receptor binding motif (aa 483–485), and the so-called “fusion-peptide proximal region”. In particular, these last two S regions are known to be involved in the human receptor ACE2 recognition and membrane fusion. Our structural evidence, therefore, is likely involved in the observed different transmissibility of these S mutants. Finally, we highlighted the role of glycans in the increased RBD flexibility of the monomer in the up conformation of Omicron. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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Review

Jump to: Research, Other

46 pages, 4761 KiB

Open AccessReview

Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges

by Dimitrios Tsilingiris, Natalia G. Vallianou, Irene Karampela, Gerasimos Socrates Christodoulatos, Georgios Papavasileiou, Dimitra Petropoulou, Faidon Magkos and Maria Dalamaga

Int. J. Mol. Sci. 2023, 24(13), 10458; https://doi.org/10.3390/ijms241310458 - 21 Jun 2023

Cited by 11 | Viewed by 6904

Abstract

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be [...] Read more.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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43 pages, 2700 KiB

Open AccessReview

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast

by Alessio Danilo Inchingolo, Giuseppina Malcangi, Sabino Ceci, Assunta Patano, Alberto Corriero, Luigi Vimercati, Daniela Azzollini, Grazia Marinelli, Giovanni Coloccia, Fabio Piras, Giuseppe Barile, Vito Settanni, Antonio Mancini, Nicole De Leonardis, Grazia Garofoli, Giulia Palmieri, Ciro Gargiulo Isacco, Biagio Rapone, Arnaldo Scardapane, Luigi Curatoli, Nicola Quaranta, Mario Ribezzi, Maria Massaro, Megan Jones, Ioana Roxana Bordea, Gianluca Martino Tartaglia, Antonio Scarano, Felice Lorusso, Luigi Macchia, Angela Maria Vittoria Larocca, Sergey Khachatur Aityan, Silvio Tafuri, Pasquale Stefanizzi, Giovanni Migliore, Nicola Brienza, Gianna Dipalma, Gianfranco Favia and Francesco Inchingolo Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(15), 8485; https://doi.org/10.3390/ijms23158485 - 30 Jul 2022

Cited by 7 | Viewed by 3380

Abstract

Background: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of [...] Read more.

Background: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines’ immunization findings. Methods: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. Results: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. Conclusions: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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Other

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10 pages, 679 KiB

Open AccessPerspective

Role of the Pangolin in Origin of SARS-CoV-2: An Evolutionary Perspective

by Shishir K. Gupta, Rashmi Minocha, Prithivi Jung Thapa, Mugdha Srivastava and Thomas Dandekar

Int. J. Mol. Sci. 2022, 23(16), 9115; https://doi.org/10.3390/ijms23169115 - 14 Aug 2022

Cited by 2 | Viewed by 2548

Abstract

After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike [...] Read more.

After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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6 pages, 5292 KiB

Open AccessBrief Report

Pharmacotherapy Based on ACE2 Targeting and COVID-19 Infection

by Antonio Vitiello and Francesco Ferrara

Int. J. Mol. Sci. 2022, 23(12), 6644; https://doi.org/10.3390/ijms23126644 - 14 Jun 2022

Cited by 4 | Viewed by 1867

Abstract

The new SARS-CoV-2 coronavirus is responsible for the COVID-19 pandemic. A massive vaccination campaign, which is still ongoing, has averted most serious consequences worldwide; however, lines of research are continuing to identify the best drug therapies to treat COVID-19 infection. SARS-CoV-2 penetrates the [...] Read more.

The new SARS-CoV-2 coronavirus is responsible for the COVID-19 pandemic. A massive vaccination campaign, which is still ongoing, has averted most serious consequences worldwide; however, lines of research are continuing to identify the best drug therapies to treat COVID-19 infection. SARS-CoV-2 penetrates the cells of the host organism through ACE2. The ACE2 protein plays a key role in the renin–angiotensin system (RAS) and undergoes changes in expression during different stages of COVID-19 infection. It appears that an unregulated RAS is responsible for the severe lung damage that occurs in some cases of COVID-19. Pharmacologically modifying the expression of ACE2 could be an interesting line of research to follow in order to avoid the severe complications of COVID-19. Full article

(This article belongs to the Special Issue Genomic Variation and Epidemiology of SARS-CoV-2)

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