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Antivirals and Vaccines: Molecular Research in Treatment and Prevention
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Antivirals and Vaccines: Molecular Research in Treatment and Prevention

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 8959

Special Issue Editor

Prof. Dr. Nuno Taveira

E-Mail Website
Guest Editor
Research Institute for Medicines-FFUL (iMed.ULisboa), Universidade de Lisboa (University of Lisbon), Lisbon, Portugal
Interests: HIV; antivirals and vaccines; drug resistance; pathogenesis; antibody neutralization; virus evolution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As the HIV, HCV and SARS-Cov-2 pandemics well illustrate, antivirals or vaccines have been crucial to control transmission, prevent disease progression and avert a very significant number of deaths caused by viral infections. However, vaccines are still not available for most virus infections and diseases including those caused by HIV and HCV. Likewise, a very limited number of drugs is currently available to treat deadly viral infections such as lower respiratory infections caused by RSV, influenza viruses and coronaviruses. Moreover, drug resistance is increasing in certain viruses such as HIV threatening the success obtained so far in controlling this pandemic. New and better antiviral drugs are in need to fight this global public health threat. This special issue of the International Journal of Molecular Sciences seeks to attract top level publications on the design, development and validation of new antivirals and vaccines to treat and prevent human viral diseases. We invite you to share with us your most insightful primary research work, reviews, and hypothesis on these important topics.

Prof. Dr. Nuno Taveira
Guest Editor

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Keywords

  • antivirals
  • antiviral drugs
  • broad-spectrum antivirals
  • neutralizing antibodies
  • drug targets and mechanism of action
  • drug resistance
  • antiviral vaccines
  • vaccine immunogens
  • immunogen design
  • mRNA vaccines
  • self-amplifying mRNA vaccines
  • vaccine adjuvants
  • animal models

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Published Papers (4 papers)

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Research

21 pages, 11620 KiB  
Article
Exploring the Efficacy of Peptides and Mimics against Influenza A Virus, Adenovirus, and Murine Norovirus
by Umme Laila Urmi, Ajay Kumar Vijay, Mark D. P. Willcox, Samuel Attard, George Enninful, Naresh Kumar, Salequl Islam and Rajesh Kuppusamy
Int. J. Mol. Sci. 2024, 25(13), 7030; https://doi.org/10.3390/ijms25137030 - 27 Jun 2024
Viewed by 3129
Abstract
The ongoing battle against viral pandemics continues, with the possibility of future outbreaks. The search for effective antiviral compounds that can combat a diverse range of viruses continues to be a focal point of research. This study investigated the efficacy of two natural [...] Read more.
The ongoing battle against viral pandemics continues, with the possibility of future outbreaks. The search for effective antiviral compounds that can combat a diverse range of viruses continues to be a focal point of research. This study investigated the efficacy of two natural antimicrobial peptides (AMPs) (lactoferricin and LL-37), two synthetic AMPs (melimine and Mel4), and nine AMP mimics (758, 1091, 1096, 1083, 610, NAPL, 3-BIPL, 4-BIPL, and Sau-22) against influenza A virus strains H1N1 and H3N2, human adenovirus 5 (HAdV-5), and murine norovirus 1 (MNV-1). These compounds were tested using virus pre-treatment, cell pre-treatment, or post-cell entry treatment assays, electron microscopy, and circular dichroism (CD), alongside evaluations of cytotoxicity against the host cells. After virus pre-treatment, the AMP mimics 610 and Sau-22 had relatively low IC50 values for influenza strains H1N1 (2.35 and 6.93 µM, respectively) and H3N2 (3.7 and 5.34 µM, respectively). Conversely, natural and synthetic AMPs were not active against these strains. For the non-enveloped viruses, the AMP Mel4 and mimic 1083 had moderate activity against HAdV-5 (Mel4 IC50 = 47.4 µM; 1083 IC50 = 47.2 µM), whereas all AMPs, but none of the mimics, were active against norovirus (LL-37 IC50 = 4.2 µM; lactoferricin IC50 = 23.18 µM; melimine IC50 = 4.8 µM; Mel4 IC50 = 8.6 µM). Transmission electron microscopy demonstrated that the mimics targeted the outer envelope of influenza viruses, while the AMPs targeted the capsid of non-enveloped viruses. CD showed that Mel4 adopted an α-helical structure in a membrane mimetic environment, but mimic 758 remained unstructured. The diverse activity against different virus groups is probably influenced by charge, hydrophobicity, size, and, in the case of natural and synthetic AMPs, their secondary structure. These findings underscore the potential of peptides and mimics as promising candidates for antiviral therapeutics against both enveloped and non-enveloped viruses. Full article
(This article belongs to the Special Issue Antivirals and Vaccines: Molecular Research in Treatment and Prevention)
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19 pages, 2903 KiB  
Article
In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
by María Micaela Gonzalez, Maria Guadalupe Vizoso-Pinto, Rosa Erra-Balsells, Thomas Gensch and Franco M. Cabrerizo
Int. J. Mol. Sci. 2024, 25(9), 4966; https://doi.org/10.3390/ijms25094966 - 2 May 2024
Cited by 1 | Viewed by 1013
Abstract
Herpes simplex virus (HSV) infections are highly widespread among humans, producing symptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threatening encephalitis. At present, there are no vaccines available, and some existing antiviral treatments can be ineffective or lead to [...] Read more.
Herpes simplex virus (HSV) infections are highly widespread among humans, producing symptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threatening encephalitis. At present, there are no vaccines available, and some existing antiviral treatments can be ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In this report, the in vitro anti-HSV effect of 9,9′-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and did not impede either the attachment or penetration steps of viral particles. The antiviral effect was only exerted under the constant presence of the dimer in the incubation media, and the mechanism of action was found to involve later events of virus infection. Analysis of fluorescence lifetime imaging data showed that the nHo-dimer internalized well into the cells when present in the extracellular incubation medium, with a preferential accumulation into perinuclear organelles including mitochondria. After washing the host cells with fresh medium free of nHo-dimer, the signal decreased, suggesting the partial release of the compound from the cells. This agrees with the observation that the antiviral effect is solely manifested when the alkaloid is consistently present in the incubation media. Full article
(This article belongs to the Special Issue Antivirals and Vaccines: Molecular Research in Treatment and Prevention)
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19 pages, 5691 KiB  
Article
Generation and Characterization of Recombinant Pseudorabies Virus Delivering African Swine Fever Virus CD2v and p54
by Jianhui Wei, Chuancheng Liu, Xinyan He, Bilal Abbas, Qi Chen, Zhaolong Li and Zhihua Feng
Int. J. Mol. Sci. 2024, 25(1), 335; https://doi.org/10.3390/ijms25010335 - 26 Dec 2023
Cited by 3 | Viewed by 1621
Abstract
African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies [...] Read more.
African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies recombinant virus (PRV) expressing ASFV CD2v and p54 proteins (PRV-∆TK-(CD2v)-∆gE-(p54)) using CRISPR/Cas9 and homologous recombination technology. PRV-∆TK-(CD2v)-∆gE-(p54) effectively delivers CD2v and p54, and it exhibits reduced virulence. Immunization with PRV-∆TK-(CD2v)-∆gE-(p54) neither induces pruritus nor causes systemic infection and inflammation. Furthermore, a double knockout of the TK and gE genes eliminates the depletion of T, B, and monocytes/macrophages in the blood caused by wild-type viral infection, decreases the proliferation of granulocytes to eliminate T-cell immunosuppression from granulocytes, and enhances the ability of the immune system against PRV infection. An overexpression of CD2v and p54 proteins does not alter the characteristics of PRV-∆TK/∆gE. Moreover, PRV-∆TK-(CD2v)-∆gE-(p54) successfully induces antibody production via intramuscular (IM) vaccination and confers effective protection for vaccinated mice upon challenge. Thus, PRV-∆TK-(CD2v)-∆gE-(p54) demonstrates good immunogenicity and safety, providing highly effective protection against PRV and ASFV. It potentially represents a suitable candidate for the development of a bivalent vaccine against both PRV and ASFV infections. Full article
(This article belongs to the Special Issue Antivirals and Vaccines: Molecular Research in Treatment and Prevention)
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14 pages, 2773 KiB  
Article
An HIV-1/HIV-2 Chimeric Envelope Glycoprotein Generates Binding and Neutralising Antibodies against HIV-1 and HIV-2 Isolates
by Nuno Taveira, Inês Figueiredo, Rita Calado, Francisco Martin, Inês Bártolo, José M. Marcelino, Pedro Borrego, Fernando Cardoso and Helena Barroso
Int. J. Mol. Sci. 2023, 24(10), 9077; https://doi.org/10.3390/ijms24109077 - 22 May 2023
Viewed by 2132
Abstract
The development of immunogens that elicit broadly reactive neutralising antibodies (bNAbs) is the highest priority for an HIV vaccine. We have shown that a prime-boost vaccination strategy with vaccinia virus expressing the envelope glycoprotein gp120 of HIV-2 and a polypeptide comprising the envelope [...] Read more.
The development of immunogens that elicit broadly reactive neutralising antibodies (bNAbs) is the highest priority for an HIV vaccine. We have shown that a prime-boost vaccination strategy with vaccinia virus expressing the envelope glycoprotein gp120 of HIV-2 and a polypeptide comprising the envelope regions C2, V3 and C3 elicits bNAbs against HIV-2. We hypothesised that a chimeric envelope gp120 containing the C2, V3 and C3 regions of HIV-2 and the remaining parts of HIV-1 would elicit a neutralising response against HIV-1 and HIV-2. This chimeric envelope was synthesised and expressed in vaccinia virus. Balb/c mice primed with the recombinant vaccinia virus and boosted with an HIV-2 C2V3C3 polypeptide or monomeric gp120 from a CRF01_AG HIV-1 isolate produced antibodies that neutralised >60% (serum dilution 1:40) of a primary HIV-2 isolate. Four out of nine mice also produced antibodies that neutralised at least one HIV-1 isolate. Neutralising epitope specificity was assessed using a panel of HIV-1 TRO.11 pseudoviruses with key neutralising epitopes disrupted by alanine substitution (N160A in V2; N278A in the CD4 binding site region; N332A in the high mannose patch). The neutralisation of the mutant pseudoviruses was reduced or abolished in one mouse, suggesting that neutralising antibodies target the three major neutralising epitopes in the HIV-1 envelope gp120. These results provide proof of concept for chimeric HIV-1/HIV-2 envelope glycoproteins as vaccine immunogens that can direct the antibody response against neutralising epitopes in the HIV-1 and HIV-2 surface glycoproteins. Full article
(This article belongs to the Special Issue Antivirals and Vaccines: Molecular Research in Treatment and Prevention)
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