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The most promising strategies for defeating coronavirus are vaccines and antivirals, review shows

Gene therapy delivered through the adeno-associated virus is likely the most attractive alternative treatment until a vaccine is produced.

Jeff Lagasse, Associate Editor

In an unprecedented effort, hundreds of thousands of researchers and clinicians worldwide are locked in a race against time to develop cures, vaccines, and better diagnostic tests for COVID-19, the illness caused by the virus SARS-CoV-2.

More than 1,650 articles on COVID-19 are already listed in databases such as Google Scholar, while dozens more are added daily. The register ClinicalTrials.gov lists over 460 ongoing clinical trials on COVID-19, although the majority are still in the earliest stages. Given the diversity of experimental approaches among these studies, a systematic review of possible clinical strategies is timely -- and comes in the form of a new study published in Frontiers in Microbiology.

In it, experts from the University of North Carolina at Chapel Hill reviewed possible strategies against dangerous coronaviruses -- not only SARS-CoV-2 and its relatives such as SARS-Cov and MERS-Cov, but also as yet unknown strains that will inevitably emerge in the future.

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They propose that the most promising approaches for fast progress are selected antivirals such as remdesivir, as well as gene therapy.

WHAT'S THE IMPACT

The authors discuss, one-by-one, the possible strategies against the coronavirus. First and most effective are 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. 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.

Because the amino acid sequence of the S-protein is very different across coronaviruses (for instance, there's a 76-78% similarity between SARS-Cov and SARS-Cov-2), vaccines against one strain typically won't work against another. But because the development and testing of new vaccines takes one to several years, other approaches are essential in the meantime.

The second-most effective treatments are likely broad-spectrum antivirals such as nucleoside analogs, 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 analogs don't work well. Exceptions seem to be β-D-N4-hydroxycytidine and remdesivir, proposed by the authors as good candidates against SARS-Cov-2.

Third is convalescent blood plasma from patients who have recovered, with low levels of a range of antibodies against the virus; or preferably, monoclonal antibodies, isolated and mass-produced through biotechnology, which are slower to develop. Such "passive immunization" can give short-term immunity.

The last approach is gene therapy delivered through the adeno-associated virus, which the authors view as the most attractive alternative until a vaccine is produced. This would entail the fast, targeted delivery of antibodies, immunoadhesins, antiviral peptides and immunomodulators to the upper airways to give short-term protection. Because of the rapid turnover of cells here, risks of toxicity are minimal. It's estimated that such tools can be developed, adapted, and tested within a month.

THE LARGER TREND

On April 14, a new public health tool called World Without COVID launched with the goal of connecting patients to coronavirus clinical trials across the country. The new product, which is powered by digital clinical trial company Clara Health, is aimed at helping propel clinical research and treatment surrounding the virus.

Today the United States has the highest number of confirmed cases, at 870,468, according to the Johns Hopkins University coronavirus tracker. Innovators, scientists and clinicians are looking for ways to treat and prevent the virus. The FDA has issued Emergency Use Authorizations for various medical devices, personal protective equipment and two types of controversial antimalarial drugs.

Twitter: @JELagasse

Email the writer: jeff.lagasse@himssmedia.com