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- J. Fros (Netherlands)
Novel Approaches to Virus Control
- J. Fros (Netherlands)
MACROCYCLES TARGETING INFLUENZA VIRUS HA SHOW ANTIVIRAL EFFECTS BY HAMPERING ADSORPTION AND FUSION, WHICH RESULT IN VIVO ANTIVIRAL EFFECTS IN MURINE AND MACAQUE MODEL
- M. Kohara (Japan)
Abstract
Background and Aims
The influenza A virus is a great public health issue. Most anti-influenza drugs currently used, such as oseltamivir and zanamivir, inhibit the enzymatic activity of neuraminidase (NA). NA inhibitor-resistant viruses, however, have already been isolated among seasonal H1N1 pandemic (H1N1) 2009, and even highly pathogenic avian H5N1 viruses. These resistant viruses can only be controlled by a new antiviral with a mechanism of action that is totally different from NA inhibition.
Methods
To devise smaller molecules capable of binding to the influenza viral HA as potential antiviral agents, we used an emerging technology called Random non-standard Peptides Integrated Discovery (RaPID). Sequencing of 69 molecular clones from the selected cDNAs revealed 28 candidates for an inhibitor of HA (iHA).
Results
Of the 28 candidates, eight iHA macrocycles inhibited plaque formation of the high pathogenic H5N1 avian virus . Among these macrocycles, iHA-24 and iHA-100 remarkably reduced the plaque number and size. Virus replication was inhibited by iHA-100 treatment at −1 h, 0 h, 0.3 h, 1 h, and 1.5 h after infection, but uncoating at 3 h after infection was not inhibited. They showed powerful efficacy in preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models.
Conclusions
iHA-100 is a candidate antiviral agent that inhibited both virus replication and pathogenesis in vivo. The RaPID system can attain a broader anti-viral spectrum of macrocycles. Thus, building on this current work, we expect that more potent, broad-spectrum anti-influenza macrocycles will be developed in the near future.
DELIVERY OF A COVID-19 VACCINE TO THE SKIN USING A HIGH DENSITY-MICROARRAY PATCH (HD-MAP)
- P. R. Young (Australia)
Abstract
Background and Aims
SARS-CoV-2 has infected hundreds of millions globally and resulted in nearly 6 million deaths to date, with ongoing waves of infection in communities with relatively high vaccination rates. We still face many challenges in the rollout of vaccines and subsequent boosting of initial protective immune responses. A high-density microarray patch (HD-MAP) has been developed at the University of Queensland and Vaxxas that can deliver vaccines to the skin, with significant dose sparing and high thermostability.
Methods
This presentation will cover the background HD-MAP technology and its application to COVID-19 vaccine development. We have used the HD-MAP to deliver a SARS-CoV-2 spike subunit vaccine directly to the skin of mice in order to examine protective efficacy.
Results
We have shown that the vaccine, dry-coated on the patch is thermostable, and delivery of spike via HD-MAP induces higher cellular and antibody immune responses than traditional needle delivery, with serum able to potently neutralize clinically relevant isolates including alpha, beta, delta and omicron lineages. Finally, a single dose of HD-MAP-delivered spike provided complete protection from a lethal virus challenge.
Conclusions
We have shown that HD-MAP delivery of a SARS-CoV-2 vaccine has the potential to significantly impact the ongoing COVID-19 pandemic.
IN VITRO ANTIVIRAL ACTIVITY OF SOLANUM OVALIFOLIUM A NATIVE COLOMBIAN PLANT AGAINST DENV, ZIKV AND CHIKV
- E. V. Jiménez Posada (Colombia)
Abstract
Background and Aims
Background. Diseases caused by viruses (DENV, ZIKV, and CHIKV) are a global public health problem since there are no specific treatments. The major source of molecules of pharmacological interest have been natural products, and despite Colombia's biodiversity, few studies evaluate their antiviral potential.
Objective
To evaluate the in vitro antiviral potential of methanolic extract and fractions obtained from Solanum ovalifolium native from Colombian coffee region belonging to the Solanaceae family.
Methods
The extract viability was assessed by the MTT method in serial dilutions (7.8µg/mL to 500µg/mL). Screening for antiviral activity against (CHIKV/Col, ZIKV/Col, and DENV-2/S16803) was performed in vitro with a combined strategy on VERO cells, quantifying the number of infectious viral particles by plating supernatants.
Results
The methanolic extract of Solanum ovalifolium exhibited a high antiviral activity with 100% of inhibition against the three arboviruses. Afterward, we analyzed the chemical compounds in this extract by TLC, finding steroidal-like compounds, alkaloids, and polyphenols. Subsequently, we fractionated the extract using a sintered funnel and different solvents (hexane-Fraction A, ethyl acetate-Fraction B and, methanol-Fraction C). Finally, the fraction C showed antiviral activity against DENV, ZIKV, and CHIKV with inhibition of 54.67%, 61.1% and 92.3%, respectively. Next studies will focus on isolate these molecules and evaluate again the antiviral activity.
Conclusions
Solanum ovalifolium is a potential source of compounds with anti-arbovirus activity.
Acknowledge
Founded by the Universidad Cooperativa de Colombia and FCTel of the SGR-Colombia