What SARS-CoV-2 Variants Have Taught Us: Evolutionary Challenges of RNA Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (30 December 2022) | Viewed by 91904

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Master of Pharmaceutical Science Program, College of Graduate Studies, California Northstate University, Elk Grove, CA, USA
Interests: viral hepatitis; DAA; liver cancer; novel therapies; lipid metabolism; emerging infections
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Professor of Genetics, College of Biotechnology, Misr University for Science & Technology, 6th of October, Egypt
Interests: viral genetics; RNA viruses; viral hepatitis

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Dear Colleagues,

RNA viruses have a rapid pace of evolutionary change. Mutations in RNA viral genomes occur at a pace that greatly exceeds that observed in other organisms and determine much of their evolutionary “behavior”. For instance, RNA viruses have a great ability to cross species barriers and, hence, emerging new human and animal viruses. Indeed, emerging RNA viruses are currently the biggest health threat to humankind to emerge in a very long time. Thus, it is crucial at this time to shed some light on how the evolutionary behavior of RNA viruses shapes their epidemiolocal, fitness, and pathological features. This will contribute toward a better understanding of how to deal with these threats.

Dr. Ahmed Elshamy
Prof. Dr. Mohamed M. Ibrahim
Guest Editors

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Keywords

  • RNA virus
  • mutations
  • emerging viruses
  • coronaviruses

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Published Papers (25 papers)

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Editorial

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4 pages, 174 KiB  
Editorial
What SARS-CoV-2 Variants Have Taught Us: Evolutionary Challenges of RNA Viruses
by Shymaa E. Bilasy, Tutik Sri Wahyuni, Mohamed Ibrahim and Ahmed El-Shamy
Viruses 2024, 16(1), 139; https://doi.org/10.3390/v16010139 - 18 Jan 2024
Viewed by 1093
Abstract
Since its discovery in 2019, SARS-CoV-2 still makes the headline news [...] Full article

Research

Jump to: Editorial, Review, Other

17 pages, 1471 KiB  
Article
Combined Use of RT-qPCR and NGS for Identification and Surveillance of SARS-CoV-2 Variants of Concern in Residual Clinical Laboratory Samples in Miami-Dade County, Florida
by Yamina L. Carattini, Anthony Griswold, Sion Williams, Ranjini Valiathan, Yi Zhou, Bhavarth Shukla, Lilian M. Abbo, Katiuska Parra, Merce Jorda, Stephen D. Nimer, Corneliu Sologon, Hilma R. Gallegos, Roy E. Weiss, Tanira Ferreira, Abdul Memon, Peter G. Paige, Emmanuel Thomas and David M. Andrews
Viruses 2023, 15(3), 593; https://doi.org/10.3390/v15030593 - 21 Feb 2023
Cited by 4 | Viewed by 2507
Abstract
Over the course of the COVID-19 pandemic, SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and immune escape capabilities, such as Delta and Omicron, have triggered waves of new COVID-19 infections worldwide, and Omicron subvariants continue to represent a global health concern. Tracking [...] Read more.
Over the course of the COVID-19 pandemic, SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and immune escape capabilities, such as Delta and Omicron, have triggered waves of new COVID-19 infections worldwide, and Omicron subvariants continue to represent a global health concern. Tracking the prevalence and dynamics of VOCs has clinical and epidemiological significance and is essential for modeling the progression and evolution of the COVID-19 pandemic. Next generation sequencing (NGS) is recognized as the gold standard for genomic characterization of SARS-CoV-2 variants, but it is labor and cost intensive and not amenable to rapid lineage identification. Here we describe a two-pronged approach for rapid, cost-effective surveillance of SARS-CoV-2 VOCs by combining reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) and periodic NGS with the ARTIC sequencing method. Variant surveillance by RT-qPCR included the commercially available TaqPath COVID-19 Combo Kit to track S-gene target failure (SGTF) associated with the spike protein deletion H69-V70, as well as two internally designed and validated RT-qPCR assays targeting two N-terminal-domain (NTD) spike gene deletions, NTD156-7 and NTD25-7. The NTD156-7 RT-qPCR assay facilitated tracking of the Delta variant, while the NTD25-7 RT-qPCR assay was used for tracking Omicron variants, including the BA.2, BA.4, and BA.5 lineages. In silico validation of the NTD156-7 and NTD25-7 primers and probes compared with publicly available SARS-CoV-2 genome databases showed low variability in regions corresponding to oligonucleotide binding sites. Similarly, in vitro validation with NGS-confirmed samples showed excellent correlation. RT-qPCR assays allow for near-real-time monitoring of circulating and emerging variants allowing for ongoing surveillance of variant dynamics in a local population. By performing periodic sequencing of variant surveillance by RT-qPCR methods, we were able to provide ongoing validation of the results obtained by RT-qPCR screening. Rapid SARS-CoV-2 variant identification and surveillance by this combined approach served to inform clinical decisions in a timely manner and permitted better utilization of sequencing resources. Full article
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19 pages, 1347 KiB  
Article
The Outcome of BNT162b2, ChAdOx1-Sand mRNA-1273 Vaccines and Two Boosters: A Prospective Longitudinal Real-World Study
by Sanaa M. Kamal, Moheyeldeen Mohamed Naghib, Moataz Daadour, Mansour N. Alsuliman, Ziad G. Alanazi, Abdulaziz Abdullah Basalem, Abdulaziz M. Alaskar and Khaled Saed
Viruses 2023, 15(2), 326; https://doi.org/10.3390/v15020326 - 24 Jan 2023
Cited by 1 | Viewed by 2381
Abstract
To date, the effectiveness of COVID-19 vaccines and booster doses has yet to be evaluated in longitudinal head-to-head studies. This single-center longitudinal study assessed the effectiveness of ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273 vaccines and assessed two BNT162b2 boosters in 1550 participants, of whom [...] Read more.
To date, the effectiveness of COVID-19 vaccines and booster doses has yet to be evaluated in longitudinal head-to-head studies. This single-center longitudinal study assessed the effectiveness of ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273 vaccines and assessed two BNT162b2 boosters in 1550 participants, of whom 26% had comorbidities. In addition, the SARS-CoV-2 antibody dynamics was monitored. A group of 1500 unvaccinated subjects was included as the controls. The study’s endpoint was the development of virologically-proven COVID-19 cases after vaccine completion, while the secondary endpoint was hospitalizations due to severe COVID-19. Overall, 23 (4.6%), 16 (3%), and 18 (3.8%) participants vaccinated with ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273, respectively, developed COVID-19 after vaccine completion, with an effectiveness of 89%, 92%, and 90%. Ten COVID-19 cases were reported in participants with comorbidities, three of whom were hospitalized. No hospitalizations occurred after boosters. SARS-CoV-2 antibody levels peaked 2–4 weeks after the second vaccine dose but declined after a mean of 28.50 ± 3.48 weeks. Booster doses significantly enhanced antibody responses. Antibody titers ≤ 154 U/mL were associated with a higher risk of COVID-19 emergence. Thus, COVID-19 vaccines effectively reduced COVID-19 and prevented severe disease. The vaccine-induced SARS-CoV-2 antibody responses declined after 28–32 weeks. Booster doses induced significant maintained responses. SARS-CoV-2 antibody levels may help determine the timing and need for vaccine booster doses. Full article
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13 pages, 2174 KiB  
Article
Omicron Waves in Argentina: Dynamics of SARS-CoV-2 Lineages BA.1, BA.2 and the Emerging BA.2.12.1 and BA.4/BA.5
by Carolina Torres, Mercedes Nabaes Jodar, Dolores Acuña, Romina Micaela Zambrana Montaño, Andrés Carlos Alberto Culasso, Ariel Fernando Amadio, Paula Aulicino, Santiago Ceballos, Marco Cacciabue, Humberto Debat, María José Dus Santos, María Florencia Eberhardt, Carlos Espul, Fabián Fay, María Ailén Fernández, Franco Fernández, Juan Manuel Fernandez Muñoz, Florencia Ferrini, Fernando Gallego, Adriana Angélica Giri, Agustina Cerri, Elisa Bolatti, María Ines Gismondi, Stephanie Goya, Iván Gramundi, José Matías Irazoqui, Guido Alberto König, Viviana Leiva, Horacio Lucero, Nathalie Marquez, Cristina Nardi, Belén Ortiz, Luis Pianciola, Carolina Beatriz Pintos, Andrea Fabiana Puebla, Carolina Victoria Rastellini, Alejandro Ezequiel Rojas, Javier Sfalcin, Ariel Suárez, Estefanía Tittarelli, Rosana Toro, Gabriela Vanina Villanova, María Cecilia Ziehm, María Carla Zimmermann, Sebastián Zunino, Proyecto PAIS Working Group, Laura Valinotto and Mariana Viegasadd Show full author list remove Hide full author list
Viruses 2023, 15(2), 312; https://doi.org/10.3390/v15020312 - 22 Jan 2023
Cited by 9 | Viewed by 3200
Abstract
The COVID-19 pandemic has lately been driven by Omicron. This work aimed to study the dynamics of SARS-CoV-2 Omicron lineages during the third and fourth waves of COVID-19 in Argentina. Molecular surveillance was performed on 3431 samples from Argentina, between EW44/2021 and EW31/2022. [...] Read more.
The COVID-19 pandemic has lately been driven by Omicron. This work aimed to study the dynamics of SARS-CoV-2 Omicron lineages during the third and fourth waves of COVID-19 in Argentina. Molecular surveillance was performed on 3431 samples from Argentina, between EW44/2021 and EW31/2022. Sequencing, phylogenetic and phylodynamic analyses were performed. A differential dynamic between the Omicron waves was found. The third wave was associated with lineage BA.1, characterized by a high number of cases, very fast displacement of Delta, doubling times of 3.3 days and a low level of lineage diversity and clustering. In contrast, the fourth wave was longer but associated with a lower number of cases, initially caused by BA.2, and later by BA.4/BA.5, with doubling times of about 10 days. Several BA.2 and BA.4/BA.5 sublineages and introductions were detected, although very few clusters with a constrained geographical distribution were observed, suggesting limited transmission chains. The differential dynamic could be due to waning immunity and an increase in population gatherings in the BA.1 wave, and a boosted population (for vaccination or recent prior immunity for BA.1 infection) in the wave caused by BA2/BA.4/BA.5, which may have limited the establishment of the new lineages. Full article
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18 pages, 3680 KiB  
Article
Humoral Immune Response Profile of COVID-19 Reveals Severity and Variant-Specific Epitopes: Lessons from SARS-CoV-2 Peptide Microarray
by Arup Acharjee, Arka Ray, Akanksha Salkar, Surbhi Bihani, Chaitanya Tuckley, Jayanthi Shastri, Sachee Agrawal, Siddhartha Duttagupta and Sanjeeva Srivastava
Viruses 2023, 15(1), 248; https://doi.org/10.3390/v15010248 - 15 Jan 2023
Cited by 5 | Viewed by 3197
Abstract
The amaranthine scale of the COVID-19 pandemic and unpredictable disease severity is of grave concern. Serological diagnostic aids are an excellent choice for clinicians for rapid and easy prognosis of the disease. To this end, we studied the humoral immune response to SARS-CoV-2 [...] Read more.
The amaranthine scale of the COVID-19 pandemic and unpredictable disease severity is of grave concern. Serological diagnostic aids are an excellent choice for clinicians for rapid and easy prognosis of the disease. To this end, we studied the humoral immune response to SARS-CoV-2 infection to map immunogenic regions in the SARS-CoV-2 proteome at amino acid resolution using a high-density SARS-CoV-2 proteome peptide microarray. The microarray has 4932 overlapping peptides printed in duplicates spanning the entire SARS-CoV-2 proteome. We found 204 and 676 immunogenic peptides against IgA and IgG, corresponding to 137 and 412 IgA and IgG epitopes, respectively. Of these, 6 and 307 epitopes could discriminate between disease severity. The emergence of variants has added to the complexity of the disease. Using the mutation panel available, we could detect 5 and 10 immunogenic peptides against IgA and IgG with mutations belonging to SAR-CoV-2 variants. The study revealed severity-based epitopes that could be presented as potential prognostic serological markers. Further, the mutant epitope immunogenicity could indicate the putative use of these markers for diagnosing variants responsible for the infection. Full article
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11 pages, 1122 KiB  
Article
Severity of COVID-19 among Hospitalized Patients: Omicron Remains a Severe Threat for Immunocompromised Hosts
by Louis Nevejan, Sien Ombelet, Lies Laenen, Els Keyaerts, Thomas Demuyser, Lucie Seyler, Oriane Soetens, Els Van Nedervelde, Reinout Naesens, Dieter Geysels, Walter Verstrepen, Lien Cattoir, Steven Martens, Charlotte Michel, Elise Mathieu, Marijke Reynders, Anton Evenepoel, Jorn Hellemans, Merijn Vanhee, Koen Magerman, Justine Maes, Veerle Matheeussen, Hélène Boogaerts, Katrien Lagrou, Lize Cuypers and Emmanuel Andréadd Show full author list remove Hide full author list
Viruses 2022, 14(12), 2736; https://doi.org/10.3390/v14122736 - 8 Dec 2022
Cited by 16 | Viewed by 2516
Abstract
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the general population in the context of a relatively high immunity gained through the early waves of coronavirus disease 19 (COVID-19), and vaccination campaigns. Despite this context, a significant number [...] Read more.
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the general population in the context of a relatively high immunity gained through the early waves of coronavirus disease 19 (COVID-19), and vaccination campaigns. Despite this context, a significant number of patients were hospitalized, and identifying the risk factors associated with severe disease in the Omicron era is critical for targeting further preventive, and curative interventions. We retrospectively analyzed the individual medical records of 1501 SARS-CoV-2 positive hospitalized patients between 13 December 2021, and 13 February 2022, in Belgium, of which 187 (12.5%) were infected with Delta, and 1036 (69.0%) with Omicron. Unvaccinated adults showed an increased risk of moderate/severe/critical/fatal COVID-19 (crude OR 1.54; 95% CI 1.09–2.16) compared to vaccinated patients, whether infected with Omicron or Delta. In adults infected with Omicron and moderate/severe/critical/fatal COVID-19 (n = 323), immunocompromised patients showed an increased risk of in-hospital mortality related to COVID-19 (adjusted OR 2.42; 95% CI 1.39–4.22), compared to non-immunocompromised patients. The upcoming impact of the pandemic will be defined by evolving viral variants, and the immune system status of the population. The observations support that, in the context of an intrinsically less virulent variant, vaccination and underlying patient immunity remain the main drivers of severe disease. Full article
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14 pages, 3643 KiB  
Article
Structural Characteristics of Heparin Binding to SARS-CoV-2 Spike Protein RBD of Omicron Sub-Lineages BA.2.12.1, BA.4 and BA.5
by Deling Shi, Changkai Bu, Peng He, Yuefan Song, Jonathan S. Dordick, Robert J. Linhardt, Lianli Chi and Fuming Zhang
Viruses 2022, 14(12), 2696; https://doi.org/10.3390/v14122696 - 1 Dec 2022
Cited by 10 | Viewed by 2388
Abstract
The now prevalent Omicron variant and its subvariants/sub-lineages have led to a significant increase in COVID-19 cases and raised serious concerns about increased risk of infectivity, immune evasion, and reinfection. Heparan sulfate (HS), located on the surface of host cells, plays an important [...] Read more.
The now prevalent Omicron variant and its subvariants/sub-lineages have led to a significant increase in COVID-19 cases and raised serious concerns about increased risk of infectivity, immune evasion, and reinfection. Heparan sulfate (HS), located on the surface of host cells, plays an important role as a co-receptor for virus–host cell interaction. The ability of heparin and HS to compete for binding of the SARS-CoV-2 spike (S) protein to cell surface HS illustrates the therapeutic potential of agents targeting protein–glycan interactions. In the current study, phylogenetic tree of variants and mutations in S protein receptor-binding domain (RBD) of Omicron BA.2.12.1, BA.4 and BA.5 were described. The binding affinity of Omicron S protein RBD to heparin was further investigated by surface plasmon resonance (SPR). Solution competition studies on the inhibitory activity of heparin oligosaccharides and desulfated heparins at different sites on S protein RBD–heparin interactions revealed that different sub-lineages tend to bind heparin with different chain lengths and sulfation patterns. Furthermore, blind docking experiments showed the contribution of basic amino acid residues in RBD and sulfo groups and carboxyl groups on heparin to the interaction. Finally, pentosan polysulfate and mucopolysaccharide polysulfate were evaluated for inhibition on the interaction of heparin and S protein RBD of Omicron BA.2.12.1, BA.4/BA.5, and both showed much stronger inhibition than heparin. Full article
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17 pages, 3809 KiB  
Article
SARS-CoV-2 Variants of Concern and Variations within Their Genome Architecture: Does Nucleotide Distribution and Mutation Rate Alter the Functionality and Evolution of the Virus?
by Varsha Ravi, Aparna Swaminathan, Sunita Yadav, Hemant Arya and Rajesh Pandey
Viruses 2022, 14(11), 2499; https://doi.org/10.3390/v14112499 - 11 Nov 2022
Cited by 3 | Viewed by 2368
Abstract
SARS-CoV-2 virus pathogenicity and transmissibility are correlated with the mutations acquired over time, giving rise to variants of concern (VOCs). Mutations can significantly influence the genetic make-up of the virus. Herein, we analyzed the SARS-CoV-2 genomes and sub-genomic nucleotide composition in relation to [...] Read more.
SARS-CoV-2 virus pathogenicity and transmissibility are correlated with the mutations acquired over time, giving rise to variants of concern (VOCs). Mutations can significantly influence the genetic make-up of the virus. Herein, we analyzed the SARS-CoV-2 genomes and sub-genomic nucleotide composition in relation to the mutation rate. Nucleotide percentage distributions of 1397 in-house-sequenced SARS-CoV-2 genomes were enumerated, and comparative analyses (i) within the VOCs and of (ii) recovered and mortality patients were performed. Fisher’s test was carried out to highlight the significant mutations, followed by RNA secondary structure prediction and protein modeling for their functional impacts. Subsequently, a uniform dinucleotide composition of AT and GC was found across study cohorts. Notably, the N gene was observed to have a high GC percentage coupled with a relatively higher mutation rate. Functional analysis demonstrated the N gene mutations, C29144T and G29332T, to induce structural changes at the RNA level. Protein secondary structure prediction with N gene missense mutations revealed a differential composition of alpha helices, beta sheets, and coils, whereas the tertiary structure displayed no significant changes. Additionally, the N gene CTD region displayed no mutations. The analysis highlighted the importance of N protein in viral evolution with CTD as a possible target for antiviral drugs. Full article
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14 pages, 2724 KiB  
Article
In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics
by Dhruv Chauhan, Nikhil Chakravarty, Arjit Vijey Jeyachandran, Akshaya Jayakarunakaran, Sanjeev Sinha, Rakesh Mishra, Vaithilingaraja Arumugaswami and Arunachalam Ramaiah
Viruses 2022, 14(11), 2461; https://doi.org/10.3390/v14112461 - 6 Nov 2022
Cited by 7 | Viewed by 3132
Abstract
New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic [...] Read more.
New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron’s spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome. Full article
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7 pages, 1402 KiB  
Article
Rapid Identification of SARS-CoV-2 Omicron BA.5 Spike Mutation F486V in Clinical Specimens Using a High-Resolution Melting-Based Assay
by Akira Aoki, Hirokazu Adachi, Yoko Mori, Miyabi Ito, Katsuhiko Sato, Masayoshi Kinoshita, Masahiro Kuriki, Kenji Okuda, Toru Sakakibara, Yoshinori Okamoto and Hideto Jinno
Viruses 2022, 14(11), 2401; https://doi.org/10.3390/v14112401 - 29 Oct 2022
Cited by 3 | Viewed by 2054
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.5 emerged as of February 2022 and replaced the earlier Omicron subvariants BA.1 and BA.2. COVID-19 genomic surveillance should be continued as new variants seem to subsequently appear, including post-BA.5 subvariants. A rapid assay [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.5 emerged as of February 2022 and replaced the earlier Omicron subvariants BA.1 and BA.2. COVID-19 genomic surveillance should be continued as new variants seem to subsequently appear, including post-BA.5 subvariants. A rapid assay is needed to differentiate between the currently dominant BA.5 variant and other variants. This study successfully developed a high-resolution melting (HRM)-based assay for BA.4/5-characteristic spike mutation F486V detection and demonstrated that our assay could discriminate between BA.1, BA.2, and BA.5 subvariants in clinical specimens. The mutational spectra at two regions (G446/L452 and F486) for the variant-selective HRM analysis was the focus of our assay. The mutational spectra used as the basis to identify each Omicron subvariant were as follows: BA.1 (G446S/L452/F486), BA.2 (G446/L452/F486), and BA.4/5 (G446/L452R/F486V). Upon mutation-coding RNA fragment analysis, the wild-type fragments melting curves were distinct from those of the mutant fragments. Based on the analysis of 120 clinical samples (40 each of subvariants BA.1, BA.2, and BA.5), this method’s sensitivity and specificity were determined to be more than 95% and 100%, respectively. These results clearly demonstrate that this HRM-based assay is a simple screening method for monitoring Omicron subvariant evolution. Full article
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7 pages, 845 KiB  
Communication
SARS-CoV-2: Searching for the Missing Variants
by Emilia Caputo and Luigi Mandrich
Viruses 2022, 14(11), 2364; https://doi.org/10.3390/v14112364 - 26 Oct 2022
Cited by 3 | Viewed by 1691
Abstract
Structural and phylogenetic analysis of the spike glycoprotein highlighted that the last variants, annotated as omicron, have about 30 mutations compared to the initial version reported in China, while the delta variant, supposed to be the omicron ancestor, shows only 7 mutations. Moreover, [...] Read more.
Structural and phylogenetic analysis of the spike glycoprotein highlighted that the last variants, annotated as omicron, have about 30 mutations compared to the initial version reported in China, while the delta variant, supposed to be the omicron ancestor, shows only 7 mutations. Moreover, the five omicron variants were isolated between November 2021 and January 2022, and the last variant BA.2.75, unofficially named centaurus, was isolated in May 2022. It appears that, since the isolation of the delta variant (October 2020) to the omicron BA.1 (November 2021), there was an interval of one year, whereas the five omicron variants were isolated in three months, and after a successive four months period, the BA.2.75 variant was isolated. So, what is the temporal and phylogenetic correlation among all these variants? The analysis of common mutations among delta and the omicron variants revealed: (i) a phylogenetic correlation among these variants; (ii) the existence of BA.1 and BA.2 omicron variants a few months before being isolated; (iii) at least three possible intermediate variants during the evolution of omicron; (iv) the evolution of the BA.2.12.1, BA.4 and BA.5 variants from omicron BA.2; (v) the centaurus variant evolution from omicron BA.2.12.1. Full article
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12 pages, 3174 KiB  
Article
Impact of Early Pandemic SARS-CoV-2 Lineages Replacement with the Variant of Concern P.1 (Gamma) in Western Bahia, Brazil
by Josilene R. Pinheiro, Esther C. dos Reis, Jéssica P. Farias, Mayanna M. C. Fogaça, Patrícia de S. da Silva, Itana Vivian R. Santana, Ana Luiza S. Rocha, Paloma O. Vidal, Rafael da C. Simões, Wilson B. Luiz, Alexander Birbrair, Renato S. de Aguiar, Renan P. de Souza, Vasco A. de C. Azevedo, Gepoliano Chaves, Aline Belmok, Ricardo Durães-Carvalho, Fernando L. Melo, Bergmann M. Ribeiro and Jaime Henrique Amorim
Viruses 2022, 14(10), 2314; https://doi.org/10.3390/v14102314 - 21 Oct 2022
Cited by 6 | Viewed by 2679
Abstract
Background: The correct understanding of the epidemiological dynamics of COVID-19, caused by the SARS-CoV-2, is essential for formulating public policies of disease containment. Methods: In this study, we constructed a picture of the epidemiological dynamics of COVID-19 in a Brazilian population of almost [...] Read more.
Background: The correct understanding of the epidemiological dynamics of COVID-19, caused by the SARS-CoV-2, is essential for formulating public policies of disease containment. Methods: In this study, we constructed a picture of the epidemiological dynamics of COVID-19 in a Brazilian population of almost 17000 patients in 15 months. We specifically studied the fluctuations of COVID-19 cases and deaths due to COVID-19 over time according to host gender, age, viral load, and genetic variants. Results: As the main results, we observed that the numbers of COVID-19 cases and deaths due to COVID-19 fluctuated over time and that men were the most affected by deaths, as well as those of 60 or more years old. We also observed that individuals between 30- and 44-years old were the most affected by COVID-19 cases. In addition, the viral loads in the patients’ nasopharynx were higher in the early symptomatic period. We found that early pandemic SARS-CoV-2 lineages were replaced by the variant of concern (VOC) P.1 (Gamma) in the second half of the study period, which led to a significant increase in the number of deaths. Conclusions: The results presented in this study are helpful for future formulations of efficient public policies of COVID-19 containment. Full article
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10 pages, 720 KiB  
Communication
Differences in Clinical Presentations of Omicron Infections with the Lineages BA.2 and BA.5 in Mecklenburg-Western Pomerania, Germany, between April and July 2022
by Katja Verena Goller, Juliane Moritz, Janine Ziemann, Christian Kohler, Karsten Becker, Nils-Olaf Hübner and the CoMV-Gen Study Group
Viruses 2022, 14(9), 2033; https://doi.org/10.3390/v14092033 - 13 Sep 2022
Cited by 7 | Viewed by 2272
Abstract
Knowledge on differences in the severity and symptoms of infections with the SARS-CoV-2 Omicron variants BA.2 (Pango lineage B.1.529.2) and BA.5 (Pango lineage B.1.529.5) is still scarce. We investigated epidemiological data available from the public health authorities in Mecklenburg-Western Pomerania, Northeast Germany, between [...] Read more.
Knowledge on differences in the severity and symptoms of infections with the SARS-CoV-2 Omicron variants BA.2 (Pango lineage B.1.529.2) and BA.5 (Pango lineage B.1.529.5) is still scarce. We investigated epidemiological data available from the public health authorities in Mecklenburg-Western Pomerania, Northeast Germany, between April and July 2022 retrospectively. Comparative analyses revealed significant differences between recorded symptoms of BA.2 and BA.5 infected individuals and found strong correlations of associations between symptoms. In particular, the symptoms ‘chills or sweating’, ‘freeze’ and ‘runny nose’ were more frequently reported in BA.2 infections. In contrast, ‘other clinical symptoms’ appeared more frequently in Omicron infections with BA.5. However, the results obtained in this study provide no evidence that BA.5 has a higher pathogenicity or causes a more severe course of infection than BA.2. To our knowledge, this is the first report on clinical differences between the current Omicron variants BA.2 and BA.5 using public health data. Our study highlights the value of timely investigations of data collected by public health authorities to gather detailed information on the clinical presentation of different SARS-CoV-2 subvariants at an early stage. Full article
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10 pages, 1472 KiB  
Article
Hyperimmunized Chickens Produce Neutralizing Antibodies against SARS-CoV-2
by Emily J. Aston, Michael G. Wallach, Aarthi Narayanan, Sofia Egaña-Labrin and Rodrigo A. Gallardo
Viruses 2022, 14(7), 1510; https://doi.org/10.3390/v14071510 - 9 Jul 2022
Cited by 5 | Viewed by 11113
Abstract
The novel severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV-2, is responsible for the global COVID-19 pandemic. Effective interventions are urgently needed to mitigate the effects of COVID-19 and likely require multiple strategies. Egg-extracted antibody therapies are a low-cost and scalable strategy to protect [...] Read more.
The novel severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV-2, is responsible for the global COVID-19 pandemic. Effective interventions are urgently needed to mitigate the effects of COVID-19 and likely require multiple strategies. Egg-extracted antibody therapies are a low-cost and scalable strategy to protect at-risk individuals from SARS-CoV-2 infection. Commercial laying hens were hyperimmunized against the SARS-CoV-2 S1 protein using three different S1 recombinant proteins and three different doses. Sera and egg yolk were collected at three and six weeks after the second immunization for enzyme-linked immunosorbent assay and plaque-reduction neutralization assay to determine antigen-specific antibody titers and neutralizing antibody titers, respectively. In this study we demonstrate that hens hyperimmunized against the SARS-CoV-2 recombinant S1 and receptor binding domain (RBD) proteins produced neutralizing antibodies against SARS-CoV-2. We further demonstrate that antibody production was dependent on the dose and type of antigen administered. Our data suggests that antibodies purified from the egg yolk of hyperimmunized hens can be used as immunoprophylaxis in humans at risk of exposure to SARS-CoV-2. Full article
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10 pages, 1688 KiB  
Article
Developing Pseudovirus-Based Neutralization Assay against Omicron-Included SARS-CoV-2 Variants
by Hancong Sun, Jinghan Xu, Guanying Zhang, Jin Han, Meng Hao, Zhengshan Chen, Ting Fang, Xiangyang Chi and Changming Yu
Viruses 2022, 14(6), 1332; https://doi.org/10.3390/v14061332 - 18 Jun 2022
Cited by 16 | Viewed by 4127
Abstract
The global spread of SARS-CoV-2 and its variants poses a serious threat to human health worldwide. Recently, the emergence of Omicron has presented a new challenge to the prevention and control of the COVID-19 pandemic. A convenient and reliable in vitro neutralization assay [...] Read more.
The global spread of SARS-CoV-2 and its variants poses a serious threat to human health worldwide. Recently, the emergence of Omicron has presented a new challenge to the prevention and control of the COVID-19 pandemic. A convenient and reliable in vitro neutralization assay is an important method for validating the efficiency of antibodies, vaccines, and other potential drugs. Here, we established an effective assay based on a pseudovirus carrying a full-length spike (S) protein of SARS-CoV-2 variants in the HIV-1 backbone, with a luciferase reporter gene inserted into the non-replicate pseudovirus genome. The key parameters for packaging the pseudovirus were optimized, including the ratio of the S protein expression plasmids to the HIV backbone plasmids and the collection time for the Alpha, Beta, Gamma, Kappa, and Omicron pseudovirus particles. The pseudovirus neutralization assay was validated using several approved or developed monoclonal antibodies, underscoring that Omicron can escape some neutralizing antibodies, such as REGN10987 and REGN10933, while S309 and ADG-2 still function with reduced neutralization capability. The neutralizing capacity of convalescent plasma from COVID-19 convalescent patients in Wuhan was tested against these pseudoviruses, revealing the immune evasion of Omicron. Our work established a practical pseudovirus-based neutralization assay for SARS-CoV-2 variants, which can be conducted safely under biosafety level-2 (BSL-2) conditions, and this assay will be a promising tool for studying and characterizing vaccines and therapeutic candidates against Omicron-included SARS-CoV-2 variants. Full article
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8 pages, 1036 KiB  
Communication
Omicron Sub-Lineages (BA.1.1.529 + BA.*) Current Status in Ecuador
by Andrés Carrazco-Montalvo, Andrés Herrera-Yela, Damaris Alarcón-Vallejo, Diana Gutiérrez-Pallo, Isaac Armendáriz-Castillo, Derly Andrade-Molina, Karen Muñoz-Mawyin, Juan Carlos Fernández-Cadena, Gabriel Morey-León, USFQ-COVID-19 Consortium, CRN Influenza y OVR—INSPI and Leandro Patiño
Viruses 2022, 14(6), 1177; https://doi.org/10.3390/v14061177 - 28 May 2022
Cited by 9 | Viewed by 3833
Abstract
The Omicron variant of SARS-CoV-2 is the latest pandemic lineage causing COVID-19. Despite having a vaccination rate ≥85%, Ecuador recorded a high incidence of Omicron from December 2021 to March 2022. Since Omicron emerged, it has evolved into multiple sub-lineages with distinct prevalence [...] Read more.
The Omicron variant of SARS-CoV-2 is the latest pandemic lineage causing COVID-19. Despite having a vaccination rate ≥85%, Ecuador recorded a high incidence of Omicron from December 2021 to March 2022. Since Omicron emerged, it has evolved into multiple sub-lineages with distinct prevalence in different regions. In this work, we use all Omicron sequences from Ecuador available at GISAID until March 2022 and the software Nextclade and Pangolin to identify which lineages circulate in this country. We detected 12 different sub-lineages (BA.1, BA.1.1, BA.1.1.1, BA.1.1.14, BA.1.1.2, BA.1.14, BA.1.15, BA.1.16, BA.1.17, BA.1.6, BA.2, BA.2.3), which have been reported in Africa, America, Europe, and Asia, suggesting multiple introduction events. Sub-lineages BA.1 and BA.1.1 were the most prevalent. Genomic surveillance must continue to evaluate the dynamics of current sub-lineages, the early introduction of new ones and vaccine efficacy against evolving SARS-CoV-2. Full article
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Review

Jump to: Editorial, Research, Other

19 pages, 2877 KiB  
Review
Electrostatic Surface Potential as a Key Parameter in Virus Transmission and Evolution: How to Manage Future Virus Pandemics in the Post-COVID-19 Era
by Jacques Fantini, Fodil Azzaz, Henri Chahinian and Nouara Yahi
Viruses 2023, 15(2), 284; https://doi.org/10.3390/v15020284 - 19 Jan 2023
Cited by 12 | Viewed by 4793
Abstract
Virus-cell interactions involve fundamental parameters that need to be considered in strategies implemented to control viral outbreaks. Among these, the surface electrostatic potential can give valuable information to deal with new epidemics. In this article, we describe the role of this key parameter [...] Read more.
Virus-cell interactions involve fundamental parameters that need to be considered in strategies implemented to control viral outbreaks. Among these, the surface electrostatic potential can give valuable information to deal with new epidemics. In this article, we describe the role of this key parameter in the hemagglutination of red blood cells and in the co-evolution of synaptic receptors and neurotransmitters. We then establish the functional link between lipid rafts and the electrostatic potential of viruses, with special emphasis on gangliosides, which are sialic-acid-containing, electronegatively charged plasma membrane components. We describe the common features of ganglioside binding domains, which include a wide variety of structures with little sequence homology but that possess key amino acids controlling ganglioside recognition. We analyze the role of the electrostatic potential in the transmission and intra-individual evolution of HIV-1 infections, including gatekeeper and co-receptor switch mechanisms. We show how to organize the epidemic surveillance of influenza viruses by focusing on mutations affecting the hemagglutinin surface potential. We demonstrate that the electrostatic surface potential, by modulating spike-ganglioside interactions, controls the hemagglutination properties of coronaviruses (SARS-CoV-1, MERS-CoV, and SARS-CoV-2) as well as the structural dynamics of SARS-CoV-2 evolution. We relate the broad-spectrum antiviral activity of repositioned molecules to their ability to disrupt virus-raft interactions, challenging the old concept that an antibiotic or anti-parasitic cannot also be an antiviral. We propose a new concept based on the analysis of the electrostatic surface potential to develop, in real time, therapeutic and vaccine strategies adapted to each new viral epidemic. Full article
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27 pages, 7071 KiB  
Review
A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies
by Srijan Chatterjee, Manojit Bhattacharya, Sagnik Nag, Kuldeep Dhama and Chiranjib Chakraborty
Viruses 2023, 15(1), 167; https://doi.org/10.3390/v15010167 - 5 Jan 2023
Cited by 121 | Viewed by 11268
Abstract
The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all the previously emerged variants. The numerous mutations in Omicron’s viral genome and its [...] Read more.
The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all the previously emerged variants. The numerous mutations in Omicron’s viral genome and its sub-lineages attribute it a larger amount of viral fitness, owing to the alteration of the transmission and pathophysiology of the virus. With a rapid change to the viral structure, Omicron and its sub-variants, namely BA.1, BA.2, BA.3, BA.4, and BA.5, dominate the community with an ability to escape the neutralization efficiency induced by prior vaccination or infections. Similarly, several recombinant sub-variants of Omicron, namely XBB, XBD, and XBF, etc., have emerged, which a better understanding. This review mainly entails the changes to Omicron and its sub-lineages due to it having a higher number of mutations. The binding affinity, cellular entry, disease severity, infection rates, and most importantly, the immune evading potential of them are discussed in this review. A comparative analysis of the Delta variant and the other dominating variants that evolved before Omicron gives the readers an in-depth understanding of the landscape of Omicron’s transmission and infection. Furthermore, this review discusses the range of neutralization abilities possessed by several approved antiviral therapeutic molecules and neutralizing antibodies which are functional against Omicron and its sub-variants. The rapid evolution of the sub-variants is causing infections, but the broader aspect of their transmission and neutralization has not been explored. Thus, the scientific community should adopt an elucidative approach to obtain a clear idea about the recently emerged sub-variants, including the recombinant variants, so that effective neutralization with vaccines and drugs can be achieved. This, in turn, will lead to a drop in the number of cases and, finally, an end to the pandemic. Full article
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16 pages, 853 KiB  
Review
On the Evolutionary Trajectory of SARS-CoV-2: Host Immunity as a Driver of Adaptation in RNA Viruses
by Jacob Warger and Silvana Gaudieri
Viruses 2023, 15(1), 70; https://doi.org/10.3390/v15010070 - 26 Dec 2022
Cited by 2 | Viewed by 2623
Abstract
Host immunity can exert a complex array of selective pressures on a pathogen, which can drive highly mutable RNA viruses towards viral escape. The plasticity of a virus depends on its rate of mutation, as well as the balance of fitness cost and [...] Read more.
Host immunity can exert a complex array of selective pressures on a pathogen, which can drive highly mutable RNA viruses towards viral escape. The plasticity of a virus depends on its rate of mutation, as well as the balance of fitness cost and benefit of mutations, including viral adaptations to the host’s immune response. Since its emergence, SARS-CoV-2 has diversified into genetically distinct variants, which are characterised often by clusters of mutations that bolster its capacity to escape human innate and adaptive immunity. Such viral escape is well documented in the context of other pandemic RNA viruses such as the human immunodeficiency virus (HIV) and influenza virus. This review describes the selection pressures the host’s antiviral immunity exerts on SARS-CoV-2 and other RNA viruses, resulting in divergence of viral strains into more adapted forms. As RNA viruses obscure themselves from host immunity, they uncover weak points in their own armoury that can inform more comprehensive, long-lasting, and potentially cross-protective vaccine coverage. Full article
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13 pages, 2172 KiB  
Review
The Elusive Coreceptors for the SARS-CoV-2 Spike Protein
by Reed L. Berkowitz and David A. Ostrov
Viruses 2023, 15(1), 67; https://doi.org/10.3390/v15010067 - 25 Dec 2022
Cited by 9 | Viewed by 3160
Abstract
Evidence suggests that the N-terminal domain (NTD) of the SARS-CoV-2 spike protein interacts with host coreceptors that participate in viral entry. Resolving the identity of coreceptors has important clinical implications as it may provide the basis for the development of antiviral drugs and [...] Read more.
Evidence suggests that the N-terminal domain (NTD) of the SARS-CoV-2 spike protein interacts with host coreceptors that participate in viral entry. Resolving the identity of coreceptors has important clinical implications as it may provide the basis for the development of antiviral drugs and vaccine candidates. The majority of characteristic mutations in variants of concern (VOCs) have occurred in the NTD and receptor binding domain (RBD). Unlike the RBD, mutations in the NTD have clustered in the most flexible parts of the spike protein. Many possible coreceptors have been proposed, including various sugars such as gangliosides, sialosides, and heparan sulfate. Protein coreceptors, including neuropilin-1 and leucine-rich repeat containing 15 (LRRC15), are also proposed coreceptors that engage the NTD. Full article
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21 pages, 1572 KiB  
Review
A Glimpse on the Evolution of RNA Viruses: Implications and Lessons from SARS-CoV-2
by Petra Šimičić and Snježana Židovec-Lepej
Viruses 2023, 15(1), 1; https://doi.org/10.3390/v15010001 - 20 Dec 2022
Cited by 8 | Viewed by 5800
Abstract
RNA viruses are characterised by extremely high genetic variability due to fast replication, large population size, low fidelity, and (usually) a lack of proofreading mechanisms of RNA polymerases leading to high mutation rates. Furthermore, viral recombination and reassortment may act as a significant [...] Read more.
RNA viruses are characterised by extremely high genetic variability due to fast replication, large population size, low fidelity, and (usually) a lack of proofreading mechanisms of RNA polymerases leading to high mutation rates. Furthermore, viral recombination and reassortment may act as a significant evolutionary force among viruses contributing to greater genetic diversity than obtainable by mutation alone. The above-mentioned properties allow for the rapid evolution of RNA viruses, which may result in difficulties in viral eradication, changes in virulence and pathogenicity, and lead to events such as cross-species transmissions, which are matters of great interest in the light of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemics. In this review, we aim to explore the molecular mechanisms of the variability of viral RNA genomes, emphasising the evolutionary trajectory of SARS-CoV-2 and its variants. Furthermore, the causes and consequences of coronavirus variation are explored, along with theories on the origin of human coronaviruses and features of emergent RNA viruses in general. Finally, we summarise the current knowledge on the circulating variants of concern and highlight the many unknowns regarding SARS-CoV-2 pathogenesis. Full article
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29 pages, 4224 KiB  
Review
Evolution and Control of COVID-19 Epidemic in Hong Kong
by Shuk-Ching Wong, Albert Ka-Wing Au, Janice Yee-Chi Lo, Pak-Leung Ho, Ivan Fan-Ngai Hung, Kelvin Kai-Wang To, Kwok-Yung Yuen and Vincent Chi-Chung Cheng
Viruses 2022, 14(11), 2519; https://doi.org/10.3390/v14112519 - 14 Nov 2022
Cited by 32 | Viewed by 4609
Abstract
Hong Kong SAR has adopted universal masking, social distancing, testing of all symptomatic and high-risk groups for isolation of confirmed cases in healthcare facilities, and quarantine of contacts as epidemiological control measures without city lockdown or border closure. These measures successfully suppressed the [...] Read more.
Hong Kong SAR has adopted universal masking, social distancing, testing of all symptomatic and high-risk groups for isolation of confirmed cases in healthcare facilities, and quarantine of contacts as epidemiological control measures without city lockdown or border closure. These measures successfully suppressed the community transmission of pre-Omicron SARS-CoV-2 variants or lineages during the first to the fourth wave. No nosocomial SARS-CoV-2 infection was documented among healthcare workers in the first 300 days. The strategy of COVID-19 containment was adopted to provide additional time to achieve population immunity by vaccination. The near-zero COVID-19 situation for about 8 months in 2021 did not enable adequate immunization of the eligible population. A combination of factors was identified, especially population complacency associated with the low local COVID-19 activity, together with vaccine hesitancy. The importation of the highly transmissible Omicron variant kickstarted the fifth wave of COVID-19, which could no longer be controlled by our initial measures. The explosive fifth wave, which was partially contributed by vertical airborne transmission in high-rise residential buildings, resulted in over one million cases of infection. In this review, we summarize the epidemiology of COVID-19 and the infection control and public health measures against the importation and dissemination of SARS-CoV-2 until day 1000. Full article
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Other

8 pages, 596 KiB  
Brief Report
Alpha and Omicron SARS-CoV-2 Adaptation in an Upper Respiratory Tract Model
by Gregory Mathez, Trestan Pillonel, Claire Bertelli and Valeria Cagno
Viruses 2023, 15(1), 13; https://doi.org/10.3390/v15010013 - 20 Dec 2022
Cited by 2 | Viewed by 2255
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing an unprecedented pandemic. Although vaccines and antivirals are limiting the spread, SARS-CoV-2 is still under selective pressure in human and animal populations, as demonstrated by the emergence of variants of concern. To better [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing an unprecedented pandemic. Although vaccines and antivirals are limiting the spread, SARS-CoV-2 is still under selective pressure in human and animal populations, as demonstrated by the emergence of variants of concern. To better understand the driving forces leading to new subtypes of SARS-CoV-2, we infected an ex vivo cell model of the human upper respiratory tract with Alpha and Omicron BA.1 variants for one month. Although viral RNA was detected during the entire course of the infection, infectious virus production decreased over time. Sequencing analysis did not show any adaptation in the spike protein, suggesting a key role for the adaptive immune response or adaptation to other anatomical sites for the evolution of SARS-CoV-2. Full article
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11 pages, 1212 KiB  
Brief Report
Host Cell Entry and Neutralization Sensitivity of SARS-CoV-2 Lineages B.1.620 and R.1
by Anzhalika Sidarovich, Nadine Krüger, Cheila Rocha, Luise Graichen, Amy Kempf, Inga Nehlmeier, Martin Lier, Anne Cossmann, Metodi V. Stankov, Sebastian R. Schulz, Georg M. N. Behrens, Hans-Martin Jäck, Stefan Pöhlmann and Markus Hoffmann
Viruses 2022, 14(11), 2475; https://doi.org/10.3390/v14112475 - 9 Nov 2022
Cited by 1 | Viewed by 1836
Abstract
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitates viral entry into host cells and is the key target for neutralizing antibodies. The SARS-CoV-2 lineage B.1.620 carries fifteen mutations in the S protein and is spread in Africa, the [...] Read more.
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitates viral entry into host cells and is the key target for neutralizing antibodies. The SARS-CoV-2 lineage B.1.620 carries fifteen mutations in the S protein and is spread in Africa, the US and Europe, while lineage R.1 harbors four mutations in S and infections were observed in several countries, particularly Japan and the US. However, the impact of the mutations in B.1.620 and R.1 S proteins on antibody-mediated neutralization and host cell entry are largely unknown. Here, we report that these mutations are compatible with robust ACE2 binding and entry into cell lines, and they markedly reduce neutralization by vaccine-induced antibodies. Our results reveal evasion of neutralizing antibodies by B.1.620 and R.1, which might have contributed to the spread of these lineages. Full article
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6 pages, 235 KiB  
Opinion
On the Need to Determine the Contribution of Anti-Nucleocapsid Antibodies as Potential Contributors to COVID-19 Convalescent Plasma Efficacy
by Daniele Focosi, Massimo Franchini and Arturo Casadevall
Viruses 2022, 14(11), 2378; https://doi.org/10.3390/v14112378 - 27 Oct 2022
Cited by 1 | Viewed by 1748
Abstract
Historically the therapeutic potential of polyclonal passive immunotherapies in viral diseases has been related to antiviral neutralizing antibodies, but there is also considerable evidence that non-neutralizing antibodies can translate into clinical benefit as well. In the setting of SARS-CoV-2 infection, we review here [...] Read more.
Historically the therapeutic potential of polyclonal passive immunotherapies in viral diseases has been related to antiviral neutralizing antibodies, but there is also considerable evidence that non-neutralizing antibodies can translate into clinical benefit as well. In the setting of SARS-CoV-2 infection, we review here in vitro and in vivo evidence supporting a contributing role for anti-nucleocapsid antibodies. Retrospective investigation of anti-nucleocapsid antibody levels in randomized clinical trials of COVID-19 convalescent plasma is warranted to better understand whether there is an association with efficacy or lack thereof. Full article
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