Next-Generation Vaccines and Antivirals against SARS-CoV-2

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 10042

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School of Biomedical Sciences, The University of Hong Kong, Pokfulam 999077, Hong Kong, China
Interests: molecular virology and oncology
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Special Issue Information

Dear Colleagues,

The ongoing pandemic of COVID-19 is still rapidly evolving, with an endemic tendency already in sight. Existing vaccines against SARS-CoV-2, particularly mRNA and adenoviral vectored vaccines, are highly efficacious in preventing severe disease and hospitalization. However, they are less effective in blocking transmission, and as a result, breakthrough infections are more common than expected. Historically, eradication of smallpox virus and near-eradication of poliovirus from humans relied on live attenuated vaccines that can elicit mucosal and sterilizing immunity. This should be our next goal in the development of SARS-CoV-2 vaccines. In addition to live attenuated vaccines, single-cell vaccines and replication-defective vaccines might also have their own merits worthy of further exploration. On the other hand, newly discovered antivirals against SARS-CoV-2, including a nucleoside analog and a protease inhibitor, exhibit high capability in blocking SASR-CoV-2 replication. They provide new weapons to combat COVID-19 and have just begun to bring benefits to more patients with severe COVID-19. It is expected that additional new and repurposed therapeutic agents will be available in the coming months. This Special Issue will provide an outlet for exciting original research papers and high-quality reviews focusing on next-generation vaccines and antivirals against SARS-CoV-2. This collection of papers and reviews will provide a snapshot of the current research efforts and accomplishments, from which new thoughts and strategies will be developed toward putting an end to the pandemic.

Prof. Dr. Dong-Yan Jin
Guest Editor

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Keywords

  • SARS-CoV-2
  • COVID-19
  • mRNA vaccine
  • live attenuated vaccine
  • single-cycle vaccine
  • replication-defective vaccine
  • booster vaccination
  • mucosal immunity
  • sterilizing immunity
  • neutralizing antibodies
  • nucleoside analog
  • cytotoxic T lymphocyte
  • secretary immunoglobulin A

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Published Papers (3 papers)

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Research

18 pages, 2911 KiB  
Article
COVID-19 and the Importance of Being Prepared: A Multidisciplinary Strategy for the Discovery of Antivirals to Combat Pandemics
by Maria Galvez-Llompart, Riccardo Zanni, Jorge Galvez, Subhash C. Basak and Sagar M. Goyal
Biomedicines 2022, 10(6), 1342; https://doi.org/10.3390/biomedicines10061342 - 7 Jun 2022
Cited by 3 | Viewed by 2038
Abstract
During an emergency, such as a pandemic in which time and resources are extremely scarce, it is important to find effective and rapid solutions when searching for possible treatments. One possibility in this regard is the repurposing of available “on the market” drugs. [...] Read more.
During an emergency, such as a pandemic in which time and resources are extremely scarce, it is important to find effective and rapid solutions when searching for possible treatments. One possibility in this regard is the repurposing of available “on the market” drugs. This is a proof of the concept study showing the potential of a collaboration between two research groups, engaged in computer-aided drug design and control of viral infections, for the development of early strategies to combat future pandemics. We describe a QSAR (quantitative structure activity relationship) based repurposing study on molecular topology and molecular docking for identifying inhibitors of the main protease (Mpro) of SARS-CoV-2, the causative agent of COVID-19. The aim of this computational strategy was to create an agile, rapid, and efficient way to enable the selection of molecules capable of inhibiting SARS-CoV-2 protease. Molecules selected through in silico method were tested in vitro using human coronavirus 229E as a surrogate for SARS-CoV-2. Three strategies were used to screen the antiviral activity of these molecules against human coronavirus 229E in cell cultures, e.g., pre-treatment, co-treatment, and post-treatment. We found >99% of virus inhibition during pre-treatment and co-treatment and 90–99% inhibition when the molecules were applied post-treatment (after infection with the virus). From all tested compounds, Molport-046-067-769 and Molport-046-568-802 are here reported for the first time as potential anti-SARS-CoV-2 compounds. Full article
(This article belongs to the Special Issue Next-Generation Vaccines and Antivirals against SARS-CoV-2)
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23 pages, 5672 KiB  
Article
Phage Display-Derived Compounds Displace hACE2 from Its Complex with SARS-CoV-2 Spike Protein
by Marc Sevenich, Elena Thul, Nils-Alexander Lakomek, Thomas Klünemann, Maren Schubert, Federico Bertoglio, Joop van den Heuvel, Patrick Petzsch, Jeannine Mohrlüder and Dieter Willbold
Biomedicines 2022, 10(2), 441; https://doi.org/10.3390/biomedicines10020441 - 14 Feb 2022
Cited by 5 | Viewed by 2921
Abstract
Severe respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious beta-class coronavirus. Although vaccinations have shown high efficacy, the emergence of novel variants of concern (VOCs) has already exhibited traits of immune evasion. Thus, the development of tailored antiviral medications for patients with incomplete, [...] Read more.
Severe respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious beta-class coronavirus. Although vaccinations have shown high efficacy, the emergence of novel variants of concern (VOCs) has already exhibited traits of immune evasion. Thus, the development of tailored antiviral medications for patients with incomplete, inefficient, or non-existent immunization, is essential. The attachment of viral surface proteins to the cell surface is the first crucial step in the viral replication cycle, which for SARS-CoV-2 is mediated by the high affinity interaction of the viral trimeric spike with the host cell surface-located human angiotensin converting enzyme-2 (hACE2). Here, we used a novel and efficient next generation sequencing (NGS) supported phage display strategy for the selection of a set of SARS-CoV-2 receptor binding domain (RBD)-targeting peptide ligands that bind to the target protein with low µM to nM dissociation constants. Compound CVRBDL-3 inhibits the SARS-CoV-2 spike protein association to hACE2 in a concentration-dependent manner for pre- as well as post-complex formation conditions. Further rational optimization yielded a CVRBDL-3 based divalent compound, which demonstrated inhibitory efficacy with an IC50 value of 47 nM. The obtained compounds were not only efficient for the different spike constructs from the originally isolated “wt” SARS-CoV-2, but also for B.1.1.7 mutant trimeric spike protein. Our work demonstrates that phage display-derived peptide ligands are potential fusion inhibitors of viral cell entry. Moreover, we show that rational optimization of a combination of peptide sequences is a potential strategy in the further development of therapeutics for the treatment of acute COVID-19. Full article
(This article belongs to the Special Issue Next-Generation Vaccines and Antivirals against SARS-CoV-2)
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14 pages, 5440 KiB  
Article
Humoral Immune Response in IBD Patients Three and Six Months after Vaccination with the SARS-CoV-2 mRNA Vaccines mRNA-1273 and BNT162b2
by Richard Vollenberg, Phil-Robin Tepasse, Joachim Ewald Kühn, Marc Hennies, Markus Strauss, Florian Rennebaum, Tina Schomacher, Göran Boeckel, Eva Lorentzen, Arne Bokemeyer and Tobias Max Nowacki
Biomedicines 2022, 10(1), 171; https://doi.org/10.3390/biomedicines10010171 - 13 Jan 2022
Cited by 21 | Viewed by 4299
Abstract
Severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. Vaccination is considered the core approach to containing the pandemic. There is currently insufficient evidence on the efficacy of these vaccines in immunosuppressed inflammatory bowel disease (IBD) [...] Read more.
Severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. Vaccination is considered the core approach to containing the pandemic. There is currently insufficient evidence on the efficacy of these vaccines in immunosuppressed inflammatory bowel disease (IBD) patients. The aim of this study was to investigate the humoral response in immunosuppressed IBD patients after COVID-19 mRNA vaccination. In this prospective study, IgG antibody levels (AB) against the SARS-CoV-2 receptor-binding domain (spike-protein) were quantitatively determined. For assessing the potential neutralizing capacity, a SARS-CoV-2 surrogate neutralization test (sVNT) was employed in IBD patients (n = 95) and healthy controls (n = 38). Sera were examined prior to the first/second vaccination and 3/6 months after second vaccination. Patients showed lower sVNT (%) and IgG-S (AU/mL) AB both before the second vaccination (sVNT p < 0.001; AB p < 0.001) and 3 (sVNT p = 0.002; AB p = 0.001) and 6 months (sVNT p = 0.062; AB p = 0.061) after the second vaccination. Although seroconversion rates (sVNT, IgG-S) did not differ between the two groups 3 months after second vaccination, a significant difference was seen 6 months after second vaccination (sVNT p = 0.045). Before and three months after the second vaccination, patients treated with anti-tumor necrosis factor (TNF) agents showed significantly lower AB than healthy subjects. In conclusion, an early booster shot vaccination should be discussed for IBD patients on anti-TNF therapy. Full article
(This article belongs to the Special Issue Next-Generation Vaccines and Antivirals against SARS-CoV-2)
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