Gene therapy and selected antivirals such as remdesivir are the most promising approaches in the fight against COVID-19 pandemic, according to a review of studies. The study, published in the journal Frontiers in Microbiology, analysed approaches for not only SARS-CoV-2 and its relatives such as SARS-Cov that causes Severe Acute Respiratory Syndrome (SARS) and MERS-Cov that causes the Middle East Respiratory Syndrome (MERS), but also as yet unknown strains which will inevitably emerge in the future.
“Coronaviruses represent a true threat to human health and the global economy,” said Ralph Baric, a professor at the University of North Carolina in the US. “We must first consider novel countermeasures to control the SARS-Cov-2 pandemic virus and then the vast array of high-threat zoonotic viruses that are poised for human emergence in the future,” Baric said.
To help focus the global search for a treatment, the researchers aim to provide a comprehensive resource of possible lines of attack against SARS-Cov-2 and related coronaviruses. They said first, and most effective approach is using vaccines.
In the present case, the most successful are likely to carry the receptor binding domain of the virus’s S-protein, which allows it to bind to and fuse with host cells, the researchers said. Besides the traditional live attenuated, inactivated, and subunit-based vaccines, modern types such as DNA/RNA-based and nanoparticle- or viral vector-borne vaccines should be considered, they said.
The researchers noted the second-most likely effective are broad-spectrum antivirals such as nucleoside analogues, which mimic the bases in the virus’s RNA genome and get mistakenly incorporated into nascent RNA chains, stalling the copy process. But because coronaviruses have a so-called “proofreading” enzyme which can cut such mismatches out, most nucleoside analogues don’t work well, according to the researchers.
However, exceptions seem to be beta-D-N4-hydroxycytidine and remdesivir, proposed by them as good candidates against SARS-Cov-2, they said.
The researchers also analysed nonvalescent blood plasma from patients who recovered, with low levels of a range of antibodies against the virus; or preferably monoclonal antibodies, isolated and mass-produced through biotechnology. Such “passive immunisation” can give short-term immunity, the said.
The most attractive alternative until a vaccine is produced is gene therapy delivered through the adeno-associated virus (AAV), the researchers said. This would entail the fast, targeted delivery of antibodies, immunoadhesins, antiviral peptides, and immunomodulators to the upper airways, to give short-term protection, they said.
The researchers noted that because of the rapid turnover of cells here, risks of toxicity are minimal. They estimate that such tools can be developed, adapted, and tested within a month.
“AAV-based passive immunisation can be used as a quick alternative. It is straightforward and only contains two components, the viral vector and the antibody. Multiple AAV vectors have been proven to be safe and effective for human use,” said study co-author Long Ping Victor Tse.
“In theory, a single dose could mount a protective response within a week and last for more than a year. The currently high price could be reduced when treating infectious diseases, which have a larger market,” Victor Tse said.
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